False heterozygosity at chromosome X for male sample in Exome Sequencing
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4.0 years ago
koay • 0

Hi,

We found something that we think could be due to alignment error on our exome sequencing data. Reads were mapped to GRCh38 reference genome using BWA-MEM. We found several heterozygous variants on chromosome X for our male samples. Upon inspection using IGV, the reads seemed to be of good quality mapping with alternate variants found on both forward and reverse reads. However, it is unlikely for male to be heterozygous. Using RBMX gene as an example, we performed Sanger sequencing and found that all the variants are supposed to be homozygous.

Can anyone with male exome sequencing data in hand kindly take a look at RBMX gene at chrX:136874183 region. Please let me know if anyone have similar observation on their bam files using IGV. Thank you.

RBMX false heterozygosity

exome sequencing alignment • 1.1k views
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I too got heterozygous variants on X-chromosome in males cells from my WGS DNA data variant calling with GATK4.The reason is these variants lies in the psedo-autosomal regions between X and Y or there should be a homolog gene for that position.

Coming to your RBMX gene at chrX:136874183 which has a homolog RBMY gene in chry .So that may be the reason your exome reads wrongly mapped and eventually given you a heterozygous variants during variant call.That clearly reflects on your sanger sequencing

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