Variant 1-23431121-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_017707.4(ASAP3):c.2551G>A(p.Glu851Lys) variant causes a missense change. The variant allele was found at a frequency of 0.000972 in 1,585,638 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00073 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0010 ( 2 hom. )

Consequence

ASAP3
NM_017707.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.19

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 -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.031019598).

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ASAP3	NM_017707.4 link	c.2551G>A	p.Glu851Lys	missense_variant	24/25	ENST00000336689.8	NP_060177.2	Q8TDY4-1A0A024RAB1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ASAP3	ENST00000336689.8 link	c.2551G>A	p.Glu851Lys	missense_variant	24/25	1	NM_017707.4	ENSP00000338769.3		Q8TDY4-1

Frequencies

GnomAD3 genomes

AF:

0.000729

AC:

111

AN:

152242

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000458

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00126

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.000576

AC:

115

AN:

199684

Hom.:

AF XY:

0.000550

AC XY:

AN XY:

107208

show subpopulations

Gnomad AFR exome

AF:

0.000245

Gnomad AMR exome

AF:

0.000105

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000578

Gnomad NFE exome

AF:

0.00122

Gnomad OTH exome

AF:

0.000391

GnomAD4 exome

AF:

0.000998

AC:

1431

AN:

1433278

Hom.:

Cov.:

AF XY:

0.000942

AC XY:

669

AN XY:

710220

show subpopulations

Gnomad4 AFR exome

AF:

0.000181

Gnomad4 AMR exome

AF:

0.000125

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000390

Gnomad4 NFE exome

AF:

0.00123

Gnomad4 OTH exome

AF:

0.00116

GnomAD4 genome

AF:

0.000729

AC:

111

AN:

152360

Hom.:

Cov.:

AF XY:

0.000698

AC XY:

AN XY:

74512

show subpopulations

Gnomad4 AFR

AF:

0.000457

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00126

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.000875

Hom.:

Bravo

AF:

0.000676

TwinsUK

AF:

0.00162

AC:

ALSPAC

AF:

0.00130

AC:

ESP6500AA

AF:

0.000909

AC:

ESP6500EA

AF:

0.000582

AC:

ExAC

AF:

0.000424

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

Dec 21, 2023

The c.2551G>A (p.E851K) alteration is located in exon 24 (coding exon 24) of the ASAP3 gene. This alteration results from a G to A substitution at nucleotide position 2551, causing the glutamic acid (E) at amino acid position 851 to be replaced by a lysine (K). 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

0.66

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Uncertain

0.020

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.017

.;T;T;.

Eigen

Uncertain

0.28

Eigen_PC

Uncertain

0.35

FATHMM_MKL

Uncertain

0.97

M_CAP

Benign

0.022

MetaRNN

Benign

0.031

T;T;T;T

MetaSVM

Benign

-0.81

MutationAssessor

Benign

1.9

.;L;.;.

PrimateAI

Uncertain

0.72

PROVEAN

Benign

-1.2

N;N;D;N

REVEL

Benign

0.17

Sift

Uncertain

0.0020

D;D;D;D

Sift4G

Uncertain

0.011

D;T;D;T

Polyphen

1.0

.;D;.;D

Vest4

0.59

MVP

0.49

MPC

0.73

ClinPred

0.060

GERP RS

4.9

Varity_R

0.13

gMVP

0.49

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