Variant 7-23256953-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The NM_002510.3(GPNMB):c.429C>T(p.Asp143Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0338 in 1,613,802 control chromosomes in the GnomAD database, including 1,543 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.043 ( 209 hom., cov: 33)

Exomes 𝑓: 0.033 ( 1334 hom. )

Consequence

GPNMB
NM_002510.3 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.771

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.55).

BP6

Variant 7-23256953-C-T is Benign according to our data. Variant chr7-23256953-C-T is described in ClinVar as [Benign]. Clinvar id is 3055318.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=0.771 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0912 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPNMB	NM_002510.3 link	c.429C>T	p.Asp143Asp	synonymous_variant	Exon 4 of 11	ENST00000258733.9	NP_002501.1	Q14956-2Q96F58A0A024RA55

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPNMB	ENST00000258733.9 link	c.429C>T	p.Asp143Asp	synonymous_variant	Exon 4 of 11	1	NM_002510.3	ENSP00000258733.5		Q14956-2

Frequencies

GnomAD3 genomes

AF:

0.0428

AC:

6508

AN:

152120

Hom.:

209

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0539

Gnomad AMI

AF:

0.00658

Gnomad AMR

AF:

0.0445

Gnomad ASJ

AF:

0.0522

Gnomad EAS

AF:

0.00868

Gnomad SAS

AF:

0.0986

Gnomad FIN

AF:

0.0984

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.0257

Gnomad OTH

AF:

0.0402

GnomAD3 exomes

AF:

0.0465

AC:

11681

AN:

251456

Hom.:

397

AF XY:

0.0493

AC XY:

6695

AN XY:

135904

show subpopulations

Gnomad AFR exome

AF:

0.0561

Gnomad AMR exome

AF:

0.0430

Gnomad ASJ exome

AF:

0.0492

Gnomad EAS exome

AF:

0.0113

Gnomad SAS exome

AF:

0.101

Gnomad FIN exome

AF:

0.0970

Gnomad NFE exome

AF:

0.0271

Gnomad OTH exome

AF:

0.0490

GnomAD4 exome

AF:

0.0329

AC:

48020

AN:

1461564

Hom.:

1334

Cov.:

AF XY:

0.0348

AC XY:

25326

AN XY:

727102

show subpopulations

Gnomad4 AFR exome

AF:

0.0553

Gnomad4 AMR exome

AF:

0.0448

Gnomad4 ASJ exome

AF:

0.0493

Gnomad4 EAS exome

AF:

0.0193

Gnomad4 SAS exome

AF:

0.0995

Gnomad4 FIN exome

AF:

0.100

Gnomad4 NFE exome

AF:

0.0231

Gnomad4 OTH exome

AF:

0.0360

GnomAD4 genome

AF:

0.0428

AC:

6523

AN:

152238

Hom.:

209

Cov.:

AF XY:

0.0473

AC XY:

3519

AN XY:

74420

show subpopulations

Gnomad4 AFR

AF:

0.0541

Gnomad4 AMR

AF:

0.0447

Gnomad4 ASJ

AF:

0.0522

Gnomad4 EAS

AF:

0.00850

Gnomad4 SAS

AF:

0.0985

Gnomad4 FIN

AF:

0.0984

Gnomad4 NFE

AF:

0.0257

Gnomad4 OTH

AF:

0.0397

Alfa

AF:

0.0291

Hom.:

109

Bravo

AF:

0.0380

Asia WGS

AF:

0.0580

AC:

203

AN:

3478

EpiCase

AF:

0.0246

EpiControl

AF:

0.0261

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

GPNMB-related disorder

Benign:1

Feb 28, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.55

CADD

Benign

6.6

DANN

Benign

0.66

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