Variant 9-125307424-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_001282680.3(GAPVD1):c.1128C>A(p.Ala376Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0703 in 1,601,560 control chromosomes in the GnomAD database, including 4,595 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.056 ( 354 hom., cov: 32)

Exomes 𝑓: 0.072 ( 4241 hom. )

Consequence

GAPVD1
NM_001282680.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.26

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 -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.24).

BP6

Variant 9-125307424-C-A is Benign according to our data. Variant chr9-125307424-C-A is described in ClinVar as [Benign]. Clinvar id is 1250322.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.26 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.076 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GAPVD1	NM_001282680.3 linkuse as main transcript	c.1128C>A	p.Ala376Ala	synonymous_variant	7/28	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.1128C>A	p.Ala376Ala	synonymous_variant	7/28	1	NM_001282680.3	ENSP00000297933.6		Q14C86-2

Frequencies

GnomAD3 genomes

AF:

0.0560

AC:

8513

AN:

151890

Hom.:

354

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0138

Gnomad AMI

AF:

0.177

Gnomad AMR

AF:

0.0413

Gnomad ASJ

AF:

0.0375

Gnomad EAS

AF:

0.00135

Gnomad SAS

AF:

0.0649

Gnomad FIN

AF:

0.125

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0777

Gnomad OTH

AF:

0.0497

GnomAD3 exomes

AF:

0.0653

AC:

15768

AN:

241426

Hom.:

679

AF XY:

0.0662

AC XY:

8635

AN XY:

130506

show subpopulations

Gnomad AFR exome

AF:

0.0109

Gnomad AMR exome

AF:

0.0614

Gnomad ASJ exome

AF:

0.0336

Gnomad EAS exome

AF:

0.000448

Gnomad SAS exome

AF:

0.0651

Gnomad FIN exome

AF:

0.128

Gnomad NFE exome

AF:

0.0761

Gnomad OTH exome

AF:

0.0541

GnomAD4 exome

AF:

0.0718

AC:

104072

AN:

1449554

Hom.:

4241

Cov.:

AF XY:

0.0718

AC XY:

51788

AN XY:

720828

show subpopulations

Gnomad4 AFR exome

AF:

0.0103

Gnomad4 AMR exome

AF:

0.0606

Gnomad4 ASJ exome

AF:

0.0333

Gnomad4 EAS exome

AF:

0.000530

Gnomad4 SAS exome

AF:

0.0673

Gnomad4 FIN exome

AF:

0.132

Gnomad4 NFE exome

AF:

0.0759

Gnomad4 OTH exome

AF:

0.0581

GnomAD4 genome

AF:

0.0560

AC:

8508

AN:

152006

Hom.:

354

Cov.:

AF XY:

0.0569

AC XY:

4226

AN XY:

74282

show subpopulations

Gnomad4 AFR

AF:

0.0138

Gnomad4 AMR

AF:

0.0411

Gnomad4 ASJ

AF:

0.0375

Gnomad4 EAS

AF:

0.00135

Gnomad4 SAS

AF:

0.0643

Gnomad4 FIN

AF:

0.125

Gnomad4 NFE

AF:

0.0777

Gnomad4 OTH

AF:

0.0492

Alfa

AF:

0.0607

Hom.:

204

Bravo

AF:

0.0475

Asia WGS

AF:

0.0270

AC:

AN:

3478

EpiCase

AF:

0.0638

EpiControl

AF:

0.0621

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 04, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

FAM157B-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 18, 2019

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

-0.24

CADD

Benign

8.0

DANN

Benign

0.77

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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