rs370657982

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_014570.5(ARFGAP3):c.1519G>A(p.Val507Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000446 in 1,614,018 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000046 ( 0 hom. )

Consequence

ARFGAP3
NM_014570.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.00

Publications

1 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.018682063).

BP6

Variant 22-42799053-C-T is Benign according to our data. Variant chr22-42799053-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3888416.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014570.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARFGAP3	NM_014570.5	MANE Select	c.1519G>A	p.Val507Met	missense	Exon 15 of 16	NP_055385.3
	ARFGAP3	NM_001142293.2		c.1387G>A	p.Val463Met	missense	Exon 14 of 15	NP_001135765.1	Q9NP61-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ARFGAP3	ENST00000263245.10	TSL:1 MANE Select	c.1519G>A	p.Val507Met	missense	Exon 15 of 16	ENSP00000263245.5	Q9NP61-1
ARFGAP3	ENST00000437119.6	TSL:1	c.1387G>A	p.Val463Met	missense	Exon 14 of 15	ENSP00000388791.2	Q9NP61-2
ARFGAP3	ENST00000938504.1		c.1459G>A	p.Val487Met	missense	Exon 14 of 15	ENSP00000608563.1

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152160

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000676

AC:

AN:

251488

AF XY:

0.0000515

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.000992

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000352

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.0000458

AC:

AN:

1461858

Hom.:

Cov.:

AF XY:

0.0000495

AC XY:

AN XY:

727232

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33478

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00130

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53414

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000180

AC:

AN:

1111986

Other (OTH)

AF:

0.000199

AC:

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000329

AC:

AN:

152160

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74334

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41426

American (AMR)

AF:

0.00

AC:

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.00115

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5198

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68038

Other (OTH)

AF:

0.00

AC:

AN:

2086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000165

Hom.:

Bravo

AF:

0.0000227

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000824

AC:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.080

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.63

CADD

Benign

(source)

DANN

Benign

0.29

DEOGEN2

Benign

0.0055

Eigen

Benign

-1.2

Eigen_PC

Benign

-0.93

FATHMM_MKL

Benign

0.18

LIST_S2

Uncertain

0.86

M_CAP

Benign

0.0097

MetaRNN

Benign

0.019

MetaSVM

Benign

-0.92

MutationAssessor

Benign

-1.2

PhyloP100

3.0

PrimateAI

Benign

0.37

PROVEAN

Benign

1.6

REVEL

Benign

0.093

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0030

Vest4

0.20

MVP

0.21

MPC

0.090

ClinPred

0.014

GERP RS

1.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.033

gMVP

0.47

Mutation Taster

=93/7

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over