chr17-7343868-G-A

Position:

chr17-7343868-G-A

Variant summary

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

The ENST00000158762.8(ACAP1):c.581G>A(p.Arg194His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000229 in 1,613,824 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 0.000026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000023 ( 0 hom. )

Consequence

ACAP1
ENST00000158762.8 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.55

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:

ACAP1 (HGNC:):

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=0.16042584).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACAP1	NM_014716.4 linkuse as main transcript	c.581G>A	p.Arg194His	missense_variant	8/22	ENST00000158762.8	NP_055531.1	Q15027
ACAP1	XM_047437150.1 linkuse as main transcript	c.359G>A	p.Arg120His	missense_variant	8/22		XP_047293106.1
ACAP1	XM_047437151.1 linkuse as main transcript	c.359G>A	p.Arg120His	missense_variant	7/21		XP_047293107.1
ACAP1	XM_047437152.1 linkuse as main transcript	c.581G>A	p.Arg194His	missense_variant	8/18		XP_047293108.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ACAP1	ENST00000158762.8 linkuse as main transcript	c.581G>A	p.Arg194His	missense_variant	8/22	1	NM_014716.4	ENSP00000158762.3	Q15027
ACAP1	ENST00000570457.6 linkuse as main transcript	c.359G>A	p.Arg120His	missense_variant	8/8	5		ENSP00000458173.2	I3L0K9
ACAP1	ENST00000571220.1 linkuse as main transcript	n.681G>A		non_coding_transcript_exon_variant	3/5	2
ACAP1	ENST00000573893.5 linkuse as main transcript	n.430G>A		non_coding_transcript_exon_variant	5/6	3

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152122

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000400

AC:

AN:

249774

Hom.:

AF XY:

0.0000592

AC XY:

AN XY:

135198

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000116

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000163

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000888

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000226

AC:

AN:

1461584

Hom.:

Cov.:

AF XY:

0.0000316

AC XY:

AN XY:

727092

show subpopulations

Gnomad4 AFR exome

AF:

0.0000598

Gnomad4 AMR exome

AF:

0.0000672

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000255

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000270

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152240

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74444

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000453

ExAC

AF:

0.0000247

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 28, 2022

The c.581G>A (p.R194H) alteration is located in exon 8 (coding exon 8) of the ACAP1 gene. This alteration results from a G to A substitution at nucleotide position 581, causing the arginine (R) at amino acid position 194 to be replaced by a histidine (H). 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

0.081

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.46

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.054

T;.

Eigen

Benign

0.16

Eigen_PC

Benign

0.20

FATHMM_MKL

Benign

0.70

LIST_S2

Benign

0.59

T;T

M_CAP

Benign

0.0089

MetaRNN

Benign

0.16

T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

1.1

L;.

MutationTaster

Benign

0.73

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-0.50

N;.

REVEL

Benign

0.11

Sift

Uncertain

0.011

D;.

Sift4G

Uncertain

0.0090

D;D

Polyphen

0.92

P;.

Vest4

0.27

MutPred

0.56

Loss of stability (P = 0.1482);.;

MVP

0.58

MPC

0.61

ClinPred

0.11

GERP RS

4.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.16

gMVP

0.32

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