Variant chr3-195294748-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_012287.6(ACAP2):c.1736C>T(p.Thr579Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000479 in 1,608,068 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000086 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000044 ( 0 hom. )

Consequence

ACAP2
NM_012287.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.94

Variant links:

Genes affected

ACAP2 (HGNC:16469): (ArfGAP with coiled-coil, ankyrin repeat and PH domains 2) Enables GTPase activator activity. Acts upstream of or within actin filament-based process. Located in ruffle. [provided by Alliance of Genome Resources, Apr 2022]

ACAP2 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=0.13248369).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACAP2	NM_012287.6 linkuse as main transcript	c.1736C>T	p.Thr579Met	missense_variant	18/23	ENST00000326793.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
ACAP2	ENST00000326793.11 linkuse as main transcript	c.1736C>T	p.Thr579Met	missense_variant	18/23	1	NM_012287.6	P1
ACAP2	ENST00000450200.2 linkuse as main transcript	c.1841C>T	p.Thr614Met	missense_variant	19/23	5
ACAP2	ENST00000466876.2 linkuse as main transcript	c.62C>T	p.Thr21Met	missense_variant	1/5	3

Frequencies

GnomAD3 genomes

AF:

0.0000793

AC:

AN:

151364

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000243

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000398

AC:

AN:

251364

Hom.:

AF XY:

0.0000368

AC XY:

AN XY:

135854

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000528

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000439

AC:

AN:

1456590

Hom.:

Cov.:

AF XY:

0.0000497

AC XY:

AN XY:

724826

show subpopulations

Gnomad4 AFR exome

AF:

0.000180

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000507

Gnomad4 SAS exome

AF:

0.0000349

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000469

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000858

AC:

AN:

151478

Hom.:

Cov.:

AF XY:

0.000122

AC XY:

AN XY:

73990

show subpopulations

Gnomad4 AFR

AF:

0.000266

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000824

Hom.:

Bravo

AF:

0.000106

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000576

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

Jan 20, 2023

The c.1736C>T (p.T579M) alteration is located in exon 18 (coding exon 18) of the ACAP2 gene. This alteration results from a C to T substitution at nucleotide position 1736, causing the threonine (T) at amino acid position 579 to be replaced by a methionine (M). 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

0.070

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.37

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.028

T;T

Eigen

Benign

0.097

Eigen_PC

Benign

0.19

FATHMM_MKL

Uncertain

0.78

LIST_S2

Uncertain

0.88

D;D

M_CAP

Benign

0.011

MetaRNN

Benign

0.13

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.20

N;.

MutationTaster

Benign

0.98

PrimateAI

Benign

0.31

PROVEAN

Benign

-1.2

N;.

REVEL

Benign

0.11

Sift

Benign

0.15

T;.

Sift4G

Benign

0.14

T;T

Polyphen

0.71

P;.

Vest4

0.16

MVP

0.65

MPC

0.68

ClinPred

0.069

GERP RS

4.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.023

gMVP

0.29

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