Variant 1-23431706-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000336689.8(ASAP3):c.2536G>A(p.Val846Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000158 in 1,523,480 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V846F) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 30)

Exomes 𝑓: 0.00017 ( 0 hom. )

Consequence

ASAP3
ENST00000336689.8 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.61

Variant links:

Genes affected

ASAP3 (HGNC:14987): (ArfGAP with SH3 domain, ankyrin repeat and PH domain 3) This gene encodes a member of a subfamily of ADP-ribosylation factor(Arf) GTPase-activating proteins that contain additional ankyrin repeat and pleckstrin homology domains. The Arf GAP domain of this protein catalyzes the hydrolysis of GTP bound to Arf proteins. The encoded protein promotes cell differentiation and migration and has been implicated in cancer cell invasion. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2009]

ASAP3 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.067222774).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ASAP3	NM_017707.4 linkuse as main transcript	c.2536G>A	p.Val846Ile	missense_variant	23/25	ENST00000336689.8	NP_060177.2	Q8TDY4-1A0A024RAB1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ASAP3	ENST00000336689.8 linkuse as main transcript	c.2536G>A	p.Val846Ile	missense_variant	23/25	1	NM_017707.4	ENSP00000338769.3		Q8TDY4-1

Frequencies

GnomAD3 genomes

AF:

0.0000592

AC:

AN:

152066

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000578

AC:

AN:

172920

Hom.:

AF XY:

0.0000766

AC XY:

AN XY:

91352

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000501

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000139

Gnomad FIN exome

AF:

0.0000579

Gnomad NFE exome

AF:

0.0000711

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000168

AC:

231

AN:

1371296

Hom.:

Cov.:

AF XY:

0.000169

AC XY:

114

AN XY:

674878

show subpopulations

Gnomad4 AFR exome

AF:

0.0000674

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.0000495

Gnomad4 EAS exome

AF:

0.0000262

Gnomad4 SAS exome

AF:

0.0000852

Gnomad4 FIN exome

AF:

0.0000199

Gnomad4 NFE exome

AF:

0.000197

Gnomad4 OTH exome

AF:

0.000142

GnomAD4 genome

AF:

0.0000591

AC:

AN:

152184

Hom.:

Cov.:

AF XY:

0.0000672

AC XY:

AN XY:

74382

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000658

Hom.:

Bravo

AF:

0.0000567

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000519

AC:

ExAC

AF:

0.0000497

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

Aug 17, 2021

The c.2536G>A (p.V846I) alteration is located in exon 23 (coding exon 23) of the ASAP3 gene. This alteration results from a G to A substitution at nucleotide position 2536, causing the valine (V) at amino acid position 846 to be replaced by an isoleucine (I). 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

0.096

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.46

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.026

.;T;T;.

Eigen

Benign

-0.37

Eigen_PC

Benign

-0.28

FATHMM_MKL

Benign

0.40

M_CAP

Benign

0.024

MetaRNN

Benign

0.067

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

2.0

.;M;.;.

MutationTaster

Benign

0.66

D;N;N

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-0.45

N;N;N;N

REVEL

Benign

0.021

Sift

Uncertain

0.0050

D;D;D;D

Sift4G

Pathogenic

0.0

D;T;T;T

Polyphen

0.10, 0.37

.;B;.;B

Vest4

0.22

MutPred

0.19

.;Loss of loop (P = 0.1242);.;.;

MVP

0.34

MPC

0.23

ClinPred

0.096

GERP RS

3.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.051

gMVP

0.13

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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