X-13807680-C-T

Variant names:

• chrX-13807680-C-T
• rs1244158589
• NM_001001995.3:c.151G>A

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_001001995.3(GPM6B):​c.151G>A​(p.Gly51Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000119 in 1,091,118 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 3 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 0.000012 (0 hom. 3 hem.)
• Consequence: GPM6B NM_001001995.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.29

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 Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.24572143).
• BS2: High Hemizygotes in GnomAdExome4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPM6B	NM_001001995.3	c.151G>A	p.Gly51Arg	missense_variant	Exon 2 of 8	ENST00000316715.9	NP_001001995.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPM6B	ENST00000316715.9	c.151G>A	p.Gly51Arg	missense_variant	Exon 2 of 8	2	NM_001001995.3	ENSP00000316861.4

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 0.0000119 AC: 13 AN: 1091118 Hom.: 0 Cov.: 27 AF XY: 0.00000840 AC XY: 3 AN XY: 356984

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000155

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 23

Bravo AF: 0.0000151

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 08, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.151G>A (p.G51R) alteration is located in exon 2 (coding exon 2) of the GPM6B gene. This alteration results from a G to A substitution at nucleotide position 151, causing the glycine (G) at amino acid position 51 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Uncertain	0.032	T
BayesDel_noAF	Benign	-0.19
CADD	Benign	21
DANN	Benign	0.97
FATHMM_MKL	Benign	0.52	D
LIST_S2	Benign	0.77	T;T;T
M_CAP	Pathogenic	0.66	D
MetaRNN	Benign	0.25	T;T;T
MetaSVM	Uncertain	0.32	D
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	0.020	N;N;N
REVEL	Uncertain	0.35
Sift	Benign	0.31	T;T;T
Sift4G	Benign	0.99	T;T;T
Polyphen		0.0	.;B;B
Vest4		0.14
MutPred		0.30		.;Loss of loop (P = 0.0203);.;
MVP		0.77
MPC		0.89
ClinPred		0.90	D
GERP RS		4.9
gMVP		0.63

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs1244158589; hg19: chrX-13825799;