dbSNP rs1031904: ARAP3:p.Asp218His (chr5-141679591-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_022481.6(ARAP3):c.652G>C(p.Asp218His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.118 in 1,613,940 control chromosomes in the GnomAD database, including 11,938 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.095 ( 812 hom., cov: 32)

Exomes 𝑓: 0.12 ( 11126 hom. )

Consequence

ARAP3
NM_022481.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.599

Variant links:

Genes affected

ARAP3 (HGNC:24097): (ArfGAP with RhoGAP domain, ankyrin repeat and PH domain 3) This gene encodes a phosphoinositide binding protein containing ARF-GAP, RHO-GAP, RAS-associating, and pleckstrin homology domains. The ARF-GAP and RHO-GAP domains cooperate in mediating rearrangements in the cell cytoskeleton and cell shape. It is a specific PtdIns(3,4,5)P3/PtdIns(3,4)P2-stimulated Arf6-GAP protein. An alternatively spliced transcript has been found for this gene, but its biological validity has not been determined. [provided by RefSeq, Sep 2015]

ARAP3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0015562177).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.145 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARAP3	NM_022481.6 link	c.652G>C	p.Asp218His	missense_variant	Exon 4 of 33	ENST00000239440.9	NP_071926.4	Q8WWN8-1Q05CH1Q9H7C1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ARAP3	ENST00000239440.9 link	c.652G>C	p.Asp218His	missense_variant	Exon 4 of 33	1	NM_022481.6	ENSP00000239440.4	Q8WWN8-1
ARAP3	ENST00000504448.1 link	c.652G>C	p.Asp218His	missense_variant	Exon 3 of 9	1		ENSP00000421148.1	Q05CH1
ARAP3	ENST00000508305.5 link	c.418G>C	p.Asp140His	missense_variant	Exon 4 of 32	2		ENSP00000421826.1	G5E9Y3
ARAP3	ENST00000626478.2 link	c.418G>C	p.Asp140His	missense_variant	Exon 3 of 31	5		ENSP00000486980.1	G5E9Y3

Frequencies

GnomAD3 genomes

AF:

0.0955

AC:

14520

AN:

152060

Hom.:

811

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0334

Gnomad AMI

AF:

0.113

Gnomad AMR

AF:

0.0983

Gnomad ASJ

AF:

0.106

Gnomad EAS

AF:

0.0762

Gnomad SAS

AF:

0.155

Gnomad FIN

AF:

0.114

Gnomad MID

AF:

0.0633

Gnomad NFE

AF:

0.126

Gnomad OTH

AF:

0.102

GnomAD3 exomes

AF:

0.112

AC:

28199

AN:

251434

Hom.:

1770

AF XY:

0.116

AC XY:

15731

AN XY:

135898

show subpopulations

Gnomad AFR exome

AF:

0.0340

Gnomad AMR exome

AF:

0.0957

Gnomad ASJ exome

AF:

0.113

Gnomad EAS exome

AF:

0.0570

Gnomad SAS exome

AF:

0.158

Gnomad FIN exome

AF:

0.118

Gnomad NFE exome

AF:

0.124

Gnomad OTH exome

AF:

0.116

GnomAD4 exome

AF:

0.121

AC:

176396

AN:

1461762

Hom.:

11126

Cov.:

AF XY:

0.122

AC XY:

88796

AN XY:

727192

show subpopulations

Gnomad4 AFR exome

AF:

0.0314

Gnomad4 AMR exome

AF:

0.100

Gnomad4 ASJ exome

AF:

0.114

Gnomad4 EAS exome

AF:

0.104

Gnomad4 SAS exome

AF:

0.158

Gnomad4 FIN exome

AF:

0.116

Gnomad4 NFE exome

AF:

0.123

Gnomad4 OTH exome

AF:

0.112

GnomAD4 genome

AF:

0.0954

AC:

14524

AN:

152178

Hom.:

812

Cov.:

AF XY:

0.0969

AC XY:

7212

AN XY:

74392

show subpopulations

Gnomad4 AFR

AF:

0.0333

Gnomad4 AMR

AF:

0.0981

Gnomad4 ASJ

AF:

0.106

Gnomad4 EAS

AF:

0.0758

Gnomad4 SAS

AF:

0.154

Gnomad4 FIN

AF:

0.114

Gnomad4 NFE

AF:

0.126

Gnomad4 OTH

AF:

0.105

Alfa

AF:

0.0671

Hom.:

104

Bravo

AF:

0.0880

TwinsUK

AF:

0.128

AC:

474

ALSPAC

AF:

0.126

AC:

485

ESP6500AA

AF:

0.0365

AC:

161

ESP6500EA

AF:

0.120

AC:

1035

ExAC

AF:

0.113

AC:

13694

Asia WGS

AF:

0.115

AC:

400

AN:

3478

EpiCase

AF:

0.123

EpiControl

AF:

0.122

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.013

T;T;T;.

Eigen

Benign

-0.45

Eigen_PC

Benign

-0.46

FATHMM_MKL

Benign

0.44

LIST_S2

Benign

0.57

.;T;T;T

MetaRNN

Benign

0.0016

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.81

.;L;.;.

PrimateAI

Benign

0.41

PROVEAN

Benign

-1.0

N;N;.;N

REVEL

Benign

0.038

Sift

Uncertain

0.0020

D;D;.;D

Sift4G

Uncertain

0.046

D;T;D;.

Polyphen

0.75

P;B;P;.

Vest4

0.26

MPC

0.70

ClinPred

0.011

GERP RS

2.2

Varity_R

0.10

gMVP

0.32

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over