Variant 9-125302647-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001282680.3(GAPVD1):c.850G>A(p.Val284Met) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00444 in 1,613,842 control chromosomes in the GnomAD database, including 23 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0031 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0046 ( 23 hom. )

Consequence

GAPVD1
NM_001282680.3 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 7.88

Variant links:

Genes affected

GAPVD1 (HGNC:23375): (GTPase activating protein and VPS9 domains 1) Enables GTPase activating protein binding activity and guanyl-nucleotide exchange factor activity. Involved in regulation of protein transport. Located in cytosol and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

GAPVD1 links:

GAPVD1 (HGNC:):

GAPVD1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.013211578).

BP6

Variant 9-125302647-G-A is Benign according to our data. Variant chr9-125302647-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 771429.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAdExome4 at 23 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GAPVD1	NM_001282680.3 linkuse as main transcript	c.850G>A	p.Val284Met	missense_variant	5/28	ENST00000297933.11	NP_001269609.1	Q14C86-2A0A024R862

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GAPVD1	ENST00000297933.11 linkuse as main transcript	c.850G>A	p.Val284Met	missense_variant	5/28	1	NM_001282680.3	ENSP00000297933.6		Q14C86-2

Frequencies

GnomAD3 genomes

AF:

0.00308

AC:

468

AN:

152114

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00354

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.00747

Gnomad FIN

AF:

0.00141

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00469

Gnomad OTH

AF:

0.00430

GnomAD3 exomes

AF:

0.00375

AC:

944

AN:

251442

Hom.:

AF XY:

0.00407

AC XY:

553

AN XY:

135896

show subpopulations

Gnomad AFR exome

AF:

0.000800

Gnomad AMR exome

AF:

0.00278

Gnomad ASJ exome

AF:

0.0000992

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00748

Gnomad FIN exome

AF:

0.00166

Gnomad NFE exome

AF:

0.00487

Gnomad OTH exome

AF:

0.00245

GnomAD4 exome

AF:

0.00458

AC:

6693

AN:

1461610

Hom.:

Cov.:

AF XY:

0.00470

AC XY:

3418

AN XY:

727146

show subpopulations

Gnomad4 AFR exome

AF:

0.000687

Gnomad4 AMR exome

AF:

0.00275

Gnomad4 ASJ exome

AF:

0.0000765

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00781

Gnomad4 FIN exome

AF:

0.00200

Gnomad4 NFE exome

AF:

0.00491

Gnomad4 OTH exome

AF:

0.00454

GnomAD4 genome

AF:

0.00307

AC:

468

AN:

152232

Hom.:

Cov.:

AF XY:

0.00308

AC XY:

229

AN XY:

74444

show subpopulations

Gnomad4 AFR

AF:

0.000722

Gnomad4 AMR

AF:

0.00354

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.00748

Gnomad4 FIN

AF:

0.00141

Gnomad4 NFE

AF:

0.00469

Gnomad4 OTH

AF:

0.00426

Alfa

AF:

0.00422

Hom.:

Bravo

AF:

0.00300

TwinsUK

AF:

0.00458

AC:

ALSPAC

AF:

0.00493

AC:

ESP6500AA

AF:

0.000908

AC:

ESP6500EA

AF:

0.00512

AC:

ExAC

AF:

0.00404

AC:

490

Asia WGS

AF:

0.00231

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Aug 15, 2018	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jun 01, 2023	GAPVD1: PP3, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.47

BayesDel_addAF

Benign

-0.0083

BayesDel_noAF

Pathogenic

0.22

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.40

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

Eigen

Pathogenic

0.84

Eigen_PC

Pathogenic

0.87

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.93

D;D;D;D;D;D;D;.;D;D

M_CAP

Benign

0.049

MetaRNN

Benign

0.013

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

MetaSVM

Uncertain

0.16

MutationAssessor

Benign

1.4

.;L;L;.;L;.;L;L;L;.

PrimateAI

Pathogenic

0.82

PROVEAN

Uncertain

-2.4

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

REVEL

Pathogenic

0.68

Sift

Uncertain

0.0010

D;D;D;D;D;D;D;D;D;.

Sift4G

Pathogenic

0.0

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

Polyphen

0.99

D;D;D;.;D;.;D;D;D;.

Vest4

0.71

MVP

0.88

MPC

0.61

ClinPred

0.024

GERP RS

6.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.50

gMVP

0.66

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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