Variant 9-125323822-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_001282680.3(GAPVD1):c.1757T>C(p.Val586Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00362 in 1,613,532 control chromosomes in the GnomAD database, including 20 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0021 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0038 ( 19 hom. )

Consequence

GAPVD1
NM_001282680.3 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 7.60

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 -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0127188265).

BP6

Variant 9-125323822-T-C is Benign according to our data. Variant chr9-125323822-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 3039020.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Homozygotes in GnomAdExome4 at 19 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GAPVD1	NM_001282680.3 linkuse as main transcript	c.1757T>C	p.Val586Ala	missense_variant	11/28	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.1757T>C	p.Val586Ala	missense_variant	11/28	1	NM_001282680.3	ENSP00000297933.6		Q14C86-2

Frequencies

GnomAD3 genomes

AF:

0.00206

AC:

313

AN:

152230

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000772

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000377

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00401

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.00181

AC:

455

AN:

251456

Hom.:

AF XY:

0.00174

AC XY:

237

AN XY:

135902

show subpopulations

Gnomad AFR exome

AF:

0.000800

Gnomad AMR exome

AF:

0.000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000196

Gnomad FIN exome

AF:

0.000370

Gnomad NFE exome

AF:

0.00361

Gnomad OTH exome

AF:

0.00114

GnomAD4 exome

AF:

0.00379

AC:

5531

AN:

1461184

Hom.:

Cov.:

AF XY:

0.00366

AC XY:

2660

AN XY:

726936

show subpopulations

Gnomad4 AFR exome

AF:

0.000388

Gnomad4 AMR exome

AF:

0.000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000186

Gnomad4 FIN exome

AF:

0.000449

Gnomad4 NFE exome

AF:

0.00480

Gnomad4 OTH exome

AF:

0.00214

GnomAD4 genome

AF:

0.00205

AC:

313

AN:

152348

Hom.:

Cov.:

AF XY:

0.00188

AC XY:

140

AN XY:

74500

show subpopulations

Gnomad4 AFR

AF:

0.000770

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000377

Gnomad4 NFE

AF:

0.00401

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.00278

Hom.:

Bravo

AF:

0.00190

TwinsUK

AF:

0.00647

AC:

ALSPAC

AF:

0.00519

AC:

ESP6500AA

AF:

0.000908

AC:

ESP6500EA

AF:

0.00407

AC:

ExAC

AF:

0.00188

AC:

228

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00300

EpiControl

AF:

0.00320

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

GAPVD1-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 04, 2021

This variant is classified as likely 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

AlphaMissense

Pathogenic

0.93

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.20

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0066

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

Eigen

Uncertain

0.19

Eigen_PC

Uncertain

0.29

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.95

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

M_CAP

Benign

0.045

MetaRNN

Benign

0.013

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

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.14

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

PrimateAI

Pathogenic

0.88

PROVEAN

Benign

-0.59

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

REVEL

Uncertain

0.32

Sift

Benign

0.49

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

Sift4G

Benign

0.11

T;T;T;T;D;T;T;T;D

Polyphen

0.98

D;P;.;P;.;P;P;P;.

Vest4

0.79

MVP

0.52

MPC

0.89

ClinPred

0.040

GERP RS

4.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.3

Varity_R

0.11

gMVP

0.24

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