Variant 5-141655385-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The ENST00000239440.9(ARAP3):c.4126C>T(p.Arg1376Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000223 in 1,585,350 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00015 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00023 ( 0 hom. )

Consequence

ARAP3
ENST00000239440.9 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.83

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:

ARAP3 (HGNC:):

ARAP3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARAP3	NM_022481.6 linkuse as main transcript	c.4126C>T	p.Arg1376Trp	missense_variant	32/33	ENST00000239440.9	NP_071926.4	Q8WWN8-1Q05CH1Q9H7C1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARAP3	ENST00000239440.9 linkuse as main transcript	c.4126C>T	p.Arg1376Trp	missense_variant	32/33	1	NM_022481.6	ENSP00000239440.4		Q8WWN8-1

Frequencies

GnomAD3 genomes

AF:

0.000151

AC:

AN:

152096

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000661

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000220

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000128

AC:

AN:

203480

Hom.:

AF XY:

0.000129

AC XY:

AN XY:

108830

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000386

Gnomad FIN exome

AF:

0.000905

Gnomad NFE exome

AF:

0.000102

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000231

AC:

331

AN:

1433254

Hom.:

Cov.:

AF XY:

0.000259

AC XY:

184

AN XY:

709934

show subpopulations

Gnomad4 AFR exome

AF:

0.0000909

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000244

Gnomad4 FIN exome

AF:

0.000834

Gnomad4 NFE exome

AF:

0.000249

Gnomad4 OTH exome

AF:

0.000152

GnomAD4 genome

AF:

0.000151

AC:

AN:

152096

Hom.:

Cov.:

AF XY:

0.000162

AC XY:

AN XY:

74272

show subpopulations

Gnomad4 AFR

AF:

0.0000242

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000661

Gnomad4 NFE

AF:

0.000220

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000247

Hom.:

Bravo

AF:

0.000132

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000662

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 24, 2024

The c.4126C>T (p.R1376W) alteration is located in exon 32 (coding exon 31) of the ARAP3 gene. This alteration results from a C to T substitution at nucleotide position 4126, causing the arginine (R) at amino acid position 1376 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.81

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.21

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.11

T;T;T

Eigen

Uncertain

0.58

Eigen_PC

Uncertain

0.59

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.97

.;D;D

M_CAP

Benign

0.049

MetaRNN

Uncertain

0.44

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.4

.;M;.

MutationTaster

Benign

0.71

D;D;D;D

PrimateAI

Pathogenic

0.80

PROVEAN

Uncertain

-3.5

D;D;.

REVEL

Benign

0.22

Sift

Pathogenic

0.0

D;D;.

Sift4G

Uncertain

0.0030

D;D;D

Polyphen

1.0

D;D;D

Vest4

0.77

MVP

0.43

MPC

1.1

ClinPred

0.79

GERP RS

5.1

Varity_R

0.51

gMVP

0.70

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over