X-13807680-C-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

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

Scores

1
4
9

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.29
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

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
GPM6BNM_001001995.3 linkc.151G>A p.Gly51Arg missense_variant Exon 2 of 8 ENST00000316715.9 NP_001001995.1 Q13491-4

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
GPM6BENST00000316715.9 linkc.151G>A p.Gly51Arg missense_variant Exon 2 of 8 2 NM_001001995.3 ENSP00000316861.4 Q13491-4

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
show subpopulations
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
LINK: link

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1244158589; hg19: chrX-13825799; API