Variant 5-141654432-T-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_022481.6(ARAP3):c.4153A>G(p.Met1385Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000211 in 1,420,356 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

ARAP3
NM_022481.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.18

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:

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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.4153A>G	p.Met1385Val	missense_variant	33/33	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.4153A>G	p.Met1385Val	missense_variant	33/33	1	NM_022481.6	ENSP00000239440.4		Q8WWN8-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000211

AC:

AN:

1420356

Hom.:

Cov.:

AF XY:

0.00000142

AC XY:

AN XY:

702056

show subpopulations

Gnomad4 AFR exome

AF:

0.0000310

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000183

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Feb 05, 2024

The c.4153A>G (p.M1385V) alteration is located in exon 33 (coding exon 32) of the ARAP3 gene. This alteration results from a A to G substitution at nucleotide position 4153, causing the methionine (M) at amino acid position 1385 to be replaced by a valine (V). 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

Benign

0.16

BayesDel_addAF

Benign

-0.073

BayesDel_noAF

Benign

-0.34

CADD

Uncertain

DANN

Benign

0.94

DEOGEN2

Benign

0.023

T;T;T;.

Eigen

Benign

-0.16

Eigen_PC

Benign

-0.10

FATHMM_MKL

Uncertain

0.82

LIST_S2

Uncertain

0.91

.;D;D;T

M_CAP

Benign

0.024

MetaRNN

Benign

0.18

T;T;T;T

MetaSVM

Benign

-0.92

MutationAssessor

Uncertain

2.4

.;M;.;.

PrimateAI

Uncertain

0.56

PROVEAN

Benign

-1.6

N;N;.;N

REVEL

Benign

0.11

Sift

Uncertain

0.0020

D;D;.;D

Sift4G

Uncertain

0.016

D;D;D;D

Polyphen

0.77

P;B;P;.

Vest4

0.36

MutPred

0.18

.;Gain of methylation at K1386 (P = 0.0168);.;.;

MVP

0.54

MPC

0.57

ClinPred

0.83

GERP RS

2.5

Varity_R

0.58

gMVP

0.58

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.48

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.48

Position offset: -1

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over