Variant X-13816882-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP4

The NM_001001995.3(GPM6B):c.23C>A(p.Ala8Glu) variant causes a missense change. The variant allele was found at a frequency of 0.00000898 in 111,308 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000090 ( 0 hom., 1 hem., cov: 22)

Exomes 𝑓: 0.000021 ( 0 hom. 17 hem. )

Failed GnomAD Quality Control

Consequence

GPM6B
NM_001001995.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.80

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 Likely_benign. Variant got -1 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.3830257).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPM6B	NM_001001995.3 link	c.23C>A	p.Ala8Glu	missense_variant	Exon 1 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.23C>A	p.Ala8Glu	missense_variant	Exon 1 of 8	2	NM_001001995.3	ENSP00000316861.4		Q13491-4

Frequencies

GnomAD3 genomes

AF:

0.00000898

AC:

AN:

111308

Hom.:

Cov.:

AF XY:

0.0000298

AC XY:

AN XY:

33518

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000380

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000397

AC:

AN:

176374

Hom.:

AF XY:

0.0000490

AC XY:

AN XY:

61230

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000389

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000210

AC:

AN:

1094556

Hom.:

Cov.:

AF XY:

0.0000472

AC XY:

AN XY:

360250

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:

0.000410

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000218

GnomAD4 genome

AF:

0.00000898

AC:

AN:

111308

Hom.:

Cov.:

AF XY:

0.0000298

AC XY:

AN XY:

33518

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000380

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.0000659

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

May 06, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.23C>A (p.A8E) alteration is located in exon 1 (coding exon 1) of the GPM6B gene. This alteration results from a C to A substitution at nucleotide position 23, causing the alanine (A) at amino acid position 8 to be replaced by a glutamic acid (E). 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

0.17

BayesDel_addAF

Pathogenic

0.37

BayesDel_noAF

Pathogenic

0.61

CADD

Uncertain

DANN

Uncertain

0.98

DEOGEN2

Benign

0.045

.;.;T;T

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.76

T;T;T;T

M_CAP

Pathogenic

0.90

MetaRNN

Benign

0.38

T;T;T;T

MetaSVM

Pathogenic

1.0

MutationAssessor

Benign

0.55

N;N;N;.

PrimateAI

Pathogenic

0.85

PROVEAN

Benign

-0.14

N;N;N;N

REVEL

Uncertain

0.53

Sift

Uncertain

0.028

D;D;D;D

Sift4G

Benign

0.086

T;T;T;T

Polyphen

0.40, 0.075

.;B;B;.

Vest4

0.21

MutPred

0.18

Gain of loop (P = 0.0121);Gain of loop (P = 0.0121);Gain of loop (P = 0.0121);Gain of loop (P = 0.0121);

MVP

0.88

MPC

0.93

ClinPred

0.18

GERP RS

5.1

Varity_R

0.40

gMVP

0.59

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.

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