Variant X-13785650-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001001995.3(GPM6B):c.340G>A(p.Ala114Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000339 in 1,209,811 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 12 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000089 ( 0 hom., 3 hem., cov: 23)

Exomes 𝑓: 0.000028 ( 0 hom. 9 hem. )

Consequence

GPM6B
NM_001001995.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.233

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 Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.06180784).

BP6

Variant X-13785650-C-T is Benign according to our data. Variant chrX-13785650-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2411134.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAd4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GPM6B	NM_001001995.3 linkuse as main transcript	c.340G>A	p.Ala114Thr	missense_variant	3/8	ENST00000316715.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GPM6B	ENST00000316715.9 linkuse as main transcript	c.340G>A	p.Ala114Thr	missense_variant	3/8	2	NM_001001995.3	P3	Q13491-4

Frequencies

GnomAD3 genomes

AF:

0.0000894

AC:

AN:

111837

Hom.:

Cov.:

AF XY:

0.0000881

AC XY:

AN XY:

34033

show subpopulations

Gnomad AFR

AF:

0.000326

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000218

AC:

AN:

183108

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

67576

show subpopulations

Gnomad AFR exome

AF:

0.000228

Gnomad AMR exome

AF:

0.0000365

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:

0.0000282

AC:

AN:

1097922

Hom.:

Cov.:

AF XY:

0.0000248

AC XY:

AN XY:

363286

show subpopulations

Gnomad4 AFR exome

AF:

0.000871

Gnomad4 AMR exome

AF:

0.0000284

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000185

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000119

Gnomad4 OTH exome

AF:

0.000108

GnomAD4 genome

AF:

0.0000894

AC:

AN:

111889

Hom.:

Cov.:

AF XY:

0.0000880

AC XY:

AN XY:

34095

show subpopulations

Gnomad4 AFR

AF:

0.000325

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000434

Hom.:

Bravo

AF:

0.000128

ESP6500AA

AF:

0.000261

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 12, 2021

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.054

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.47

CADD

Benign

4.2

DANN

Uncertain

0.98

DEOGEN2

Benign

0.29

.;.;.;.;T;T

FATHMM_MKL

Benign

0.29

LIST_S2

Benign

0.82

T;T;T;T;T;T

M_CAP

Benign

0.073

MetaRNN

Benign

0.062

T;T;T;T;T;T

MetaSVM

Uncertain

0.043

MutationAssessor

Benign

0.060

.;.;.;.;N;.

MutationTaster

Benign

1.0

D;N;N;N;N;N

PrimateAI

Benign

0.30

PROVEAN

Benign

0.030

N;N;N;N;N;N

REVEL

Uncertain

0.33

Sift

Benign

0.52

T;T;T;T;T;T

Sift4G

Benign

0.41

T;T;T;T;T;T

Polyphen

0.0010, 0.0020, 0.0

.;B;B;B;B;.

Vest4

0.093

MVP

0.69

MPC

0.72

ClinPred

0.039

GERP RS

-2.0

Varity_R

0.053

gMVP

0.60

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