Variant 7-23254171-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2BP4BP6_Moderate

The NM_002510.3(GPNMB):c.226G>T(p.Gly76Cys) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.000133 in 1,611,980 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00013 ( 0 hom. )

Consequence

GPNMB
NM_002510.3 missense, splice_region

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 5.62

Variant links:

Genes affected

GPNMB (HGNC:4462): (glycoprotein nmb) The protein encoded by this gene is a type I transmembrane glycoprotein which shows homology to the pMEL17 precursor, a melanocyte-specific protein. GPNMB shows expression in the lowly metastatic human melanoma cell lines and xenografts but does not show expression in the highly metastatic cell lines. GPNMB may be involved in growth delay and reduction of metastatic potential. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

GPNMB links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.4109534).

BP6

Variant 7-23254171-G-T is Benign according to our data. Variant chr7-23254171-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 3067283.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GPNMB	NM_002510.3 linkuse as main transcript	c.226G>T	p.Gly76Cys	missense_variant, splice_region_variant	3/11	ENST00000258733.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GPNMB	ENST00000258733.9 linkuse as main transcript	c.226G>T	p.Gly76Cys	missense_variant, splice_region_variant	3/11	1	NM_002510.3		Q14956-2

Frequencies

GnomAD3 genomes

AF:

0.000112

AC:

AN:

152188

Hom.:

Cov.:

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:

0.000414

Gnomad FIN

AF:

0.000848

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000305

AC:

AN:

248904

Hom.:

AF XY:

0.000342

AC XY:

AN XY:

134588

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000548

Gnomad SAS exome

AF:

0.000528

Gnomad FIN exome

AF:

0.00111

Gnomad NFE exome

AF:

0.000240

Gnomad OTH exome

AF:

0.00132

GnomAD4 exome

AF:

0.000135

AC:

197

AN:

1459674

Hom.:

Cov.:

AF XY:

0.000151

AC XY:

110

AN XY:

726192

show subpopulations

Gnomad4 AFR exome

AF:

0.0000300

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000757

Gnomad4 SAS exome

AF:

0.000501

Gnomad4 FIN exome

AF:

0.00120

Gnomad4 NFE exome

AF:

0.0000576

Gnomad4 OTH exome

AF:

0.000348

GnomAD4 genome

AF:

0.000112

AC:

AN:

152306

Hom.:

Cov.:

AF XY:

0.000148

AC XY:

AN XY:

74486

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:

0.000414

Gnomad4 FIN

AF:

0.000848

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.0000981

Hom.:

Bravo

AF:

0.0000491

ExAC

AF:

0.000329

AC:

EpiCase

AF:

0.000165

EpiControl

AF:

0.000119

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Mar 01, 2024

GPNMB: BP4 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.59

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Uncertain

-0.050

Cadd

Uncertain

Dann

Uncertain

1.0

Eigen

Uncertain

0.65

Eigen_PC

Uncertain

0.56

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.88

D;D;D;D

M_CAP

Benign

0.053

MetaRNN

Benign

0.41

T;T;T;T

MetaSVM

Benign

-0.29

MutationAssessor

Pathogenic

3.3

M;M;.;.

MutationTaster

Benign

1.0

D;D;D;D;D

PrimateAI

Benign

0.45

PROVEAN

Pathogenic

-8.1

D;D;D;.

REVEL

Uncertain

0.38

Sift

Uncertain

0.0010

D;D;D;.

Sift4G

Pathogenic

0.0

D;D;D;.

Polyphen

1.0

D;D;D;.

Vest4

0.83

MVP

0.76

MPC

0.43

ClinPred

0.70

GERP RS

5.2

Varity_R

0.79

gMVP

0.82

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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