Genetic Variant ASAP3:p.Ala717Asp (chr1-23433250-G-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_017707.4(ASAP3):c.2150C>A(p.Ala717Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00595 in 1,608,862 control chromosomes in the GnomAD database, including 40 homozygotes. 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 Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A717T) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0051 ( 6 hom., cov: 32)

Exomes 𝑓: 0.0060 ( 34 hom. )

Consequence

ASAP3
NM_017707.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.98

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 Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004719794).

BP6

Variant 1-23433250-G-T is Benign according to our data. Variant chr1-23433250-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 2638482.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ASAP3	NM_017707.4 link	c.2150C>A	p.Ala717Asp	missense_variant	Exon 22 of 25	ENST00000336689.8	NP_060177.2	Q8TDY4-1A0A024RAB1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ASAP3	ENST00000336689.8 link	c.2150C>A	p.Ala717Asp	missense_variant	Exon 22 of 25	1	NM_017707.4	ENSP00000338769.3		Q8TDY4-1

Frequencies

GnomAD3 genomes

AF:

0.00508

AC:

773

AN:

152190

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00138

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0110

Gnomad ASJ

AF:

0.0291

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.000471

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00626

Gnomad OTH

AF:

0.00526

GnomAD3 exomes

AF:

0.00517

AC:

1277

AN:

246950

Hom.:

AF XY:

0.00506

AC XY:

677

AN XY:

133922

show subpopulations

Gnomad AFR exome

AF:

0.00146

Gnomad AMR exome

AF:

0.00640

Gnomad ASJ exome

AF:

0.0279

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00132

Gnomad FIN exome

AF:

0.000510

Gnomad NFE exome

AF:

0.00595

Gnomad OTH exome

AF:

0.00780

GnomAD4 exome

AF:

0.00604

AC:

8797

AN:

1456554

Hom.:

Cov.:

AF XY:

0.00588

AC XY:

4255

AN XY:

723974

show subpopulations

Gnomad4 AFR exome

AF:

0.00124

Gnomad4 AMR exome

AF:

0.00653

Gnomad4 ASJ exome

AF:

0.0282

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00144

Gnomad4 FIN exome

AF:

0.000656

Gnomad4 NFE exome

AF:

0.00645

Gnomad4 OTH exome

AF:

0.00691

GnomAD4 genome

AF:

0.00508

AC:

773

AN:

152308

Hom.:

Cov.:

AF XY:

0.00483

AC XY:

360

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.00137

Gnomad4 AMR

AF:

0.0110

Gnomad4 ASJ

AF:

0.0291

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.000471

Gnomad4 NFE

AF:

0.00626

Gnomad4 OTH

AF:

0.00520

Alfa

AF:

0.00674

Hom.:

Bravo

AF:

0.00527

TwinsUK

AF:

0.00620

AC:

ALSPAC

AF:

0.00960

AC:

ESP6500AA

AF:

0.00159

AC:

ESP6500EA

AF:

0.00745

AC:

ExAC

AF:

0.00456

AC:

553

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.00692

EpiControl

AF:

0.00753

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

May 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

ASAP3: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.12

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.034

.;T;T;.

Eigen

Benign

-0.55

Eigen_PC

Benign

-0.48

FATHMM_MKL

Pathogenic

0.97

M_CAP

Benign

0.023

MetaRNN

Benign

0.0047

T;T;T;T

MetaSVM

Benign

-0.85

MutationAssessor

Uncertain

2.5

.;M;.;.

PrimateAI

Benign

0.29

PROVEAN

Benign

-1.3

N;N;D;N

REVEL

Uncertain

0.32

Sift

Uncertain

0.0010

D;D;D;D

Sift4G

Uncertain

0.018

D;T;D;T

Polyphen

0.88, 0.98

.;P;.;D

Vest4

0.41

MVP

0.44

MPC

0.55

ClinPred

0.058

GERP RS

3.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.13

gMVP

0.46

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