11-72702968-C-T

Variant names:

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001040118.3(ARAP1):c.2104G>A(p.Ala702Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000445 in 1,572,582 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000035 ( 0 hom. )

Consequence

ARAP1
NM_001040118.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.06

Variant links:

Genes affected

ARAP1 (HGNC:16925): (ArfGAP with RhoGAP domain, ankyrin repeat and PH domain 1) The protein encoded by this gene contains SAM, ARF-GAP, RHO-GAP, ankyrin repeat, RAS-associating, and pleckstrin homology (PH) domains. In vitro, this protein displays RHO-GAP and phosphatidylinositol (3,4,5) trisphosphate (PIP3)-dependent ARF-GAP activity. The encoded protein associates with the Golgi, and the ARF-GAP activity mediates changes in the Golgi and the formation of filopodia. It is thought to regulate the cell-specific trafficking of a receptor protein involved in apoptosis. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2008]

ARAP1 links:

ARAP1-AS2 (HGNC:39994): (ARAP1 antisense RNA 2)

ARAP1-AS2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.18864614).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARAP1	NM_001040118.3 link	c.2104G>A	p.Ala702Thr	missense_variant	Exon 15 of 35	ENST00000393609.8	NP_001035207.1	Q96P48-6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARAP1	ENST00000393609.8 link	c.2104G>A	p.Ala702Thr	missense_variant	Exon 15 of 35	2	NM_001040118.3	ENSP00000377233.3		Q96P48-6

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152158

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

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

GnomAD3 exomes

AF:

0.0000109

AC:

AN:

183842

Hom.:

AF XY:

0.00

AC XY:

AN XY:

98850

show subpopulations

Gnomad AFR exome

AF:

0.000193

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000352

AC:

AN:

1420424

Hom.:

Cov.:

AF XY:

0.00000285

AC XY:

AN XY:

702786

show subpopulations

Gnomad4 AFR exome

AF:

0.0000612

Gnomad4 AMR exome

AF:

0.0000264

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:

0.00

Gnomad4 OTH exome

AF:

0.0000340

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152158

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74324

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000282

Hom.:

Bravo

AF:

0.0000340

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 02, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2104G>A (p.A702T) alteration is located in exon 15 (coding exon 13) of the ARAP1 gene. This alteration results from a G to A substitution at nucleotide position 2104, causing the alanine (A) at amino acid position 702 to be replaced by a threonine (T). 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

0.11

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.45

CADD

Uncertain

DANN

Benign

0.89

DEOGEN2

Benign

0.098

.;.;.;T;T;.

Eigen

Benign

-0.099

Eigen_PC

Benign

-0.13

FATHMM_MKL

Uncertain

0.85

LIST_S2

Benign

0.84

T;T;T;T;T;T

M_CAP

Benign

0.0098

MetaRNN

Benign

0.19

T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.2

M;.;.;M;.;.

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-1.2

N;N;N;N;N;N

REVEL

Benign

0.14

Sift

Benign

0.28

T;T;T;T;T;T

Sift4G

Uncertain

0.0050

D;T;T;D;T;T

Polyphen

0.99

D;P;.;P;P;.

Vest4

0.23

MutPred

0.42

Gain of phosphorylation at A702 (P = 0.0567);.;.;Gain of phosphorylation at A702 (P = 0.0567);.;.;

MVP

0.23

MPC

0.41

ClinPred

0.21

GERP RS

3.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Varity_R

0.13

gMVP

0.19

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.13

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