Variant X-13783390-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001001995.3(GPM6B):c.500C>T(p.Ala167Val) variant causes a missense change. The variant allele was found at a frequency of 0.000000923 in 1,083,985 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 24)

Exomes 𝑓: 9.2e-7 ( 0 hom. 1 hem. )

Consequence

GPM6B
NM_001001995.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.24

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]

GPM6B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPM6B	NM_001001995.3 link	c.500C>T	p.Ala167Val	missense_variant	Exon 4 of 8	ENST00000316715.9	NP_001001995.1	Q13491-4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPM6B	ENST00000316715.9 link	c.500C>T	p.Ala167Val	missense_variant	Exon 4 of 8	2	NM_001001995.3	ENSP00000316861.4		Q13491-4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000606

AC:

AN:

165130

Hom.:

AF XY:

0.0000192

AC XY:

AN XY:

51970

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000420

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

9.23e-7

AC:

AN:

1083985

Hom.:

Cov.:

AF XY:

0.00000284

AC XY:

AN XY:

351743

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000304

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Aug 15, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.500C>T (p.A167V) alteration is located in exon 4 (coding exon 4) of the GPM6B gene. This alteration results from a C to T substitution at nucleotide position 500, causing the alanine (A) at amino acid position 167 to be replaced by a valine (V). 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

AlphaMissense

Benign

0.097

BayesDel_addAF

Uncertain

0.14

BayesDel_noAF

Uncertain

-0.030

CADD

Benign

DANN

Benign

0.52

DEOGEN2

Benign

0.29

.;.;.;.;T;.;T;T

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.92

D;D;D;D;D;D;D;D

M_CAP

Pathogenic

0.85

MetaRNN

Uncertain

0.64

D;D;D;D;D;D;D;D

MetaSVM

Uncertain

0.42

MutationAssessor

Benign

0.20

.;.;.;.;N;.;.;.

PrimateAI

Uncertain

0.64

PROVEAN

Benign

0.38

N;N;N;N;N;N;N;N

REVEL

Uncertain

0.52

Sift

Benign

1.0

T;T;T;T;T;T;T;T

Sift4G

Benign

0.74

T;T;T;T;T;T;.;.

Polyphen

0.0, 0.0010

.;B;B;B;B;.;.;.

Vest4

0.27

MutPred

0.46

.;.;Gain of sheet (P = 0.0827);.;.;.;.;.;

MVP

0.60

MPC

0.76

ClinPred

0.69

GERP RS

5.2

Varity_R

0.23

gMVP

0.71

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.16

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over