rs10521636

Variant names:

• chrX-13892190-A-G
• rs10521636
• ENST00000454189.7:c.4+46317T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000454189.7(GPM6B):​c.4+46317T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.209 in 111,064 control chromosomes in the GnomAD database, including 1,979 homozygotes. There are 6,678 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 0.21 (1979 hom., 6678 hem., cov: 22)
• Consequence: GPM6B ENST00000454189.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.672
• Publications: 1 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.324 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPM6B	XM_047442007.1	c.-3227T>C		5_prime_UTR_variant	Exon 1 of 8		XP_047297963.1
GPM6B	NM_001318729.2	c.4+46317T>C		intron_variant	Intron 1 of 6		NP_001305658.1
GPM6B	NM_001001994.3	c.4+46317T>C		intron_variant	Intron 1 of 6		NP_001001994.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPM6B	ENST00000454189.7	c.4+46317T>C		intron_variant	Intron 1 of 6	1		ENSP00000389915.2
GPM6B	ENST00000398361.7	c.-198+46137T>C		intron_variant	Intron 1 of 6	2		ENSP00000381402.3

Frequencies

GnomAD3 genomes AF: 0.209 AC: 23164 AN: 111007 Hom.: 1981 Cov.: 22

Gnomad AFR AF: 0.296

Gnomad AMI AF: 0.0424

Gnomad AMR AF: 0.246

Gnomad ASJ AF: 0.215

Gnomad EAS AF: 0.102

Gnomad SAS AF: 0.343

Gnomad FIN AF: 0.149

Gnomad MID AF: 0.148

Gnomad NFE AF: 0.161

Gnomad OTH AF: 0.188

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

GnomAD4 genome AF: 0.209 AC: 23183 AN: 111064 Hom.: 1979 Cov.: 22 AF XY: 0.201 AC XY: 6678 AN XY: 33294

African (AFR) AF: 0.296 AC: 9027 AN: 30491

American (AMR) AF: 0.245 AC: 2562 AN: 10443

Ashkenazi Jewish (ASJ) AF: 0.215 AC: 566 AN: 2637

East Asian (EAS) AF: 0.101 AC: 357 AN: 3525

South Asian (SAS) AF: 0.343 AC: 892 AN: 2602

European-Finnish (FIN) AF: 0.149 AC: 888 AN: 5959

Middle Eastern (MID) AF: 0.144 AC: 31 AN: 216

European-Non Finnish (NFE) AF: 0.161 AC: 8543 AN: 53000

Other (OTH) AF: 0.191 AC: 288 AN: 1507

Alfa AF: 0.192 Hom.: 6203

Bravo AF: 0.215

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	6.1
DANN	Benign	0.26
PhyloP100		0.67
Mutation Taster		=99/1	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs10521636; hg19: chrX-13910309;