chrX-13932736-T-C

Position:

• chrX-13932736-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000454189.7(GPM6B):​c.4+5771A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.413 in 110,851 control chromosomes in the GnomAD database, including 7,216 homozygotes. There are 13,243 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.41 (7216 hom., 13243 hem., cov: 23)
• Consequence: GPM6B ENST00000454189.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0190

Genes affected

GPM6B (HGNC:4461): (glycoprotein M6B) This gene encodes a membrane glycoprotein that belongs to the proteolipid protein family. Proteolipid protein family members are expressed in most brain regions and are thought to be involved in cellular housekeeping functions such as membrane trafficking and cell-to-cell communication. This protein may also be involved in osteoblast differentiation. Alternate splicing results in multiple transcript variants. Pseudogenes of this gene are located on chromosomes Y and 22. [provided by RefSeq, Jan 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.469 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GPM6B	NM_001001994.3	c.4+5771A>G		intron_variant
GPM6B	NM_001318729.2	c.4+5771A>G		intron_variant
GPM6B	XM_011545497.3	c.4+5771A>G		intron_variant
GPM6B	XM_017029432.2	c.4+5771A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GPM6B	ENST00000454189.7	c.4+5771A>G		intron_variant		1		A1
GPM6B	ENST00000398361.7	c.-198+5591A>G		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.413 AC: 45808 AN: 110797 Hom.: 7218 Cov.: 23 AF XY: 0.400 AC XY: 13218 AN XY: 33041

Gnomad AFR AF: 0.378

Gnomad AMI AF: 0.607

Gnomad AMR AF: 0.283

Gnomad ASJ AF: 0.473

Gnomad EAS AF: 0.0690

Gnomad SAS AF: 0.277

Gnomad FIN AF: 0.510

Gnomad MID AF: 0.412

Gnomad NFE AF: 0.474

Gnomad OTH AF: 0.403

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.413 AC: 45821 AN: 110851 Hom.: 7216 Cov.: 23 AF XY: 0.400 AC XY: 13243 AN XY: 33105

Gnomad4 AFR AF: 0.378

Gnomad4 AMR AF: 0.283

Gnomad4 ASJ AF: 0.473

Gnomad4 EAS AF: 0.0692

Gnomad4 SAS AF: 0.279

Gnomad4 FIN AF: 0.510

Gnomad4 NFE AF: 0.474

Gnomad4 OTH AF: 0.397

Alfa AF: 0.442 Hom.: 18037

Bravo AF: 0.395

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.7
DANN	Benign	0.60

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs6654096; hg19: chrX-13950855;