Variant chr22-42808795-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_014570.5(ARFGAP3):c.1292T>C(p.Met431Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00139 in 1,613,156 control chromosomes in the GnomAD database, including 34 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0016 ( 4 hom., cov: 31)

Exomes 𝑓: 0.0014 ( 30 hom. )

Consequence

ARFGAP3
NM_014570.5 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 8.16

Variant links:

Genes affected

ARFGAP3 (HGNC:661): (ADP ribosylation factor GTPase activating protein 3) The protein encoded by this gene is a GTPase-activating protein (GAP) that associates with the Golgi apparatus and regulates the early secretory pathway of proteins. The encoded protein promotes hydrolysis of ADP-ribosylation factor 1 (ARF1)-bound GTP, which is required for the dissociation of coat proteins from Golgi-derived membranes and vesicles. Dissociation of the coat proteins is a prerequisite for the fusion of these vesicles with target compartments. The activity of this protein is sensitive to phospholipids. Multiple transcript variants encoding different isoforms have been found for this gene. This gene was originally known as ARFGAP1, but that is now the name of a related but different gene. [provided by RefSeq, Nov 2008]

ARFGAP3 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.011156023).

BP6

Variant 22-42808795-A-G is Benign according to our data. Variant chr22-42808795-A-G is described in ClinVar as [Benign]. Clinvar id is 2653260.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARFGAP3	NM_014570.5 linkuse as main transcript	c.1292T>C	p.Met431Thr	missense_variant	13/16	ENST00000263245.10	NP_055385.3	Q9NP61-1A0A024R4U0
ARFGAP3	NM_001142293.2 linkuse as main transcript	c.1160T>C	p.Met387Thr	missense_variant	12/15		NP_001135765.1	Q9NP61-2
ARFGAP3	XM_005261525.5 linkuse as main transcript	c.1160T>C	p.Met387Thr	missense_variant	12/15		XP_005261582.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ARFGAP3	ENST00000263245.10 linkuse as main transcript	c.1292T>C	p.Met431Thr	missense_variant	13/16	1	NM_014570.5	ENSP00000263245.5	Q9NP61-1
ARFGAP3	ENST00000437119.6 linkuse as main transcript	c.1160T>C	p.Met387Thr	missense_variant	12/15	1		ENSP00000388791.2	Q9NP61-2
ARFGAP3	ENST00000453516.5 linkuse as main transcript	c.698T>C	p.Met233Thr	missense_variant	7/8	3		ENSP00000403995.1	H0Y6A0

Frequencies

GnomAD3 genomes

AF:

0.00156

AC:

237

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

Gnomad ASJ

AF:

0.0536

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000588

Gnomad OTH

AF:

0.000957

GnomAD3 exomes

AF:

0.00243

AC:

610

AN:

250824

Hom.:

AF XY:

0.00232

AC XY:

315

AN XY:

135574

show subpopulations

Gnomad AFR exome

AF:

0.0000616

Gnomad AMR exome

AF:

0.000233

Gnomad ASJ exome

AF:

0.0500

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000656

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000651

Gnomad OTH exome

AF:

0.00361

GnomAD4 exome

AF:

0.00137

AC:

2008

AN:

1460842

Hom.:

Cov.:

AF XY:

0.00141

AC XY:

1027

AN XY:

726662

show subpopulations

Gnomad4 AFR exome

AF:

0.0000896

Gnomad4 AMR exome

AF:

0.000246

Gnomad4 ASJ exome

AF:

0.0504

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000930

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000394

Gnomad4 OTH exome

AF:

0.00383

GnomAD4 genome

AF:

0.00156

AC:

237

AN:

152314

Hom.:

Cov.:

AF XY:

0.00164

AC XY:

122

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.0000722

Gnomad4 AMR

AF:

0.000392

Gnomad4 ASJ

AF:

0.0536

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000588

Gnomad4 OTH

AF:

0.000947

Alfa

AF:

0.00280

Hom.:

Bravo

AF:

0.00156

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00291

AC:

ExAC

AF:

0.00207

AC:

251

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00158

EpiControl

AF:

0.00136

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Apr 01, 2022

ARFGAP3: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Benign

-0.072

BayesDel_noAF

Uncertain

0.020

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.11

T;.

Eigen

Uncertain

0.65

Eigen_PC

Uncertain

0.64

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.95

D;D

M_CAP

Benign

0.057

MetaRNN

Benign

0.011

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.5

M;.

PrimateAI

Uncertain

0.75

PROVEAN

Pathogenic

-4.7

D;D

REVEL

Uncertain

0.44

Sift

Uncertain

0.0030

D;D

Sift4G

Uncertain

0.030

D;D

Polyphen

0.99

D;.

Vest4

0.95

MVP

0.69

MPC

0.51

ClinPred

0.11

GERP RS

5.0

Varity_R

0.73

gMVP

0.54

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