Variant 17-7346899-C-T 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_014716.4(ACAP1):c.1099C>T(p.Arg367Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000098 in 1,612,906 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 (★).

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00010 ( 0 hom. )

Consequence

ACAP1
NM_014716.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.52

Variant links:

Genes affected

ACAP1 (HGNC:16467): (ArfGAP with coiled-coil, ankyrin repeat and PH domains 1) Predicted to enable GTPase activator activity and metal ion binding activity. Predicted to be involved in protein transport and regulation of catalytic activity. Located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACAP1 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=0.11749968).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
ACAP1	NM_014716.4 linkuse as main transcript	c.1099C>T	p.Arg367Cys	missense_variant	13/22	ENST00000158762.8
ACAP1	XM_047437150.1 linkuse as main transcript	c.877C>T	p.Arg293Cys	missense_variant	13/22
ACAP1	XM_047437151.1 linkuse as main transcript	c.877C>T	p.Arg293Cys	missense_variant	12/21
ACAP1	XM_047437152.1 linkuse as main transcript	c.1099C>T	p.Arg367Cys	missense_variant	13/18

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACAP1	ENST00000158762.8 linkuse as main transcript	c.1099C>T	p.Arg367Cys	missense_variant	13/22	1	NM_014716.4	P1
ACAP1	ENST00000570439.1 linkuse as main transcript	n.1569C>T		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes

AF:

0.0000591

AC:

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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:

0.000118

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000877

AC:

AN:

250986

Hom.:

AF XY:

0.0000737

AC XY:

AN XY:

135638

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.0000463

Gnomad NFE exome

AF:

0.000150

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000102

AC:

149

AN:

1460718

Hom.:

Cov.:

AF XY:

0.0000909

AC XY:

AN XY:

726468

show subpopulations

Gnomad4 AFR exome

AF:

0.0000897

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.0000562

Gnomad4 NFE exome

AF:

0.000121

Gnomad4 OTH exome

AF:

0.000116

GnomAD4 genome

AF:

0.0000591

AC:

AN:

152188

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74350

show subpopulations

Gnomad4 AFR

AF:

0.0000241

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:

0.000118

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000774

Hom.:

Bravo

AF:

0.0000718

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.0000906

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.0000593

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

Nov 09, 2023

The c.1099C>T (p.R367C) alteration is located in exon 13 (coding exon 13) of the ACAP1 gene. This alteration results from a C to T substitution at nucleotide position 1099, causing the arginine (R) at amino acid position 367 to be replaced by a cysteine (C). 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

0.094

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.35

Cadd

Uncertain

Dann

Uncertain

1.0

DEOGEN2

Benign

0.069

Eigen

Benign

-0.26

Eigen_PC

Benign

-0.24

FATHMM_MKL

Benign

0.25

LIST_S2

Benign

0.77

M_CAP

Uncertain

0.086

MetaRNN

Benign

0.12

MetaSVM

Benign

-0.79

MutationAssessor

Benign

0.0

MutationTaster

Benign

0.99

PrimateAI

Benign

0.28

PROVEAN

Benign

-2.3

REVEL

Benign

0.16

Sift

Uncertain

0.0020

Sift4G

Benign

0.067

Polyphen

0.93

Vest4

0.17

MVP

0.58

MPC

1.1

ClinPred

0.27

GERP RS

3.6

Varity_R

0.17

gMVP

0.45

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.14

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