Variant 1-1293876-C-G 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_030649.3(ACAP3):c.2307G>C(p.Gln769His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000139 in 1,434,882 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: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

ACAP3
NM_030649.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.866

Variant links:

Genes affected

ACAP3 (HGNC:16754): (ArfGAP with coiled-coil, ankyrin repeat and PH domains 3) Predicted to enable GTPase activator activity and metal ion binding activity. Predicted to be involved in regulation of catalytic activity. Predicted to act upstream of or within neuron migration and regulation of neuron projection development. Predicted to be located in growth cone. [provided by Alliance of Genome Resources, Apr 2022]

ACAP3 links:

ACAP3 (HGNC:):

ACAP3 links:

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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=0.19553626).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACAP3	NM_030649.3 linkuse as main transcript	c.2307G>C	p.Gln769His	missense_variant	23/24	ENST00000354700.10	NP_085152.2	Q96P50-3Q8WTZ1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ACAP3	ENST00000354700.10 linkuse as main transcript	c.2307G>C	p.Gln769His	missense_variant	23/24	1	NM_030649.3	ENSP00000346733.5	Q96P50-3
ACAP3	ENST00000353662.4 linkuse as main transcript	c.2082G>C	p.Gln694His	missense_variant	20/21	1		ENSP00000321139.4	Q96P50-1
ACAP3	ENST00000467278.5 linkuse as main transcript	n.1833G>C		non_coding_transcript_exon_variant	13/14	1
ACAP3	ENST00000492936.5 linkuse as main transcript	n.3947G>C		non_coding_transcript_exon_variant	21/22	1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000921

AC:

AN:

217136

Hom.:

AF XY:

0.00

AC XY:

AN XY:

120860

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000612

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000139

AC:

AN:

1434882

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

714372

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000460

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000151

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 14, 2023

The c.2307G>C (p.Q769H) alteration is located in exon 23 (coding exon 23) of the ACAP3 gene. This alteration results from a G to C substitution at nucleotide position 2307, causing the glutamine (Q) at amino acid position 769 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

0.17

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.51

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.031

T;.

Eigen

Benign

-0.32

Eigen_PC

Benign

-0.30

FATHMM_MKL

Benign

0.59

LIST_S2

Uncertain

0.90

D;D

M_CAP

Benign

0.039

MetaRNN

Benign

0.20

T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.4

L;.

PrimateAI

Uncertain

0.70

PROVEAN

Benign

-0.55

N;N

REVEL

Benign

0.047

Sift

Uncertain

0.0080

D;D

Sift4G

Uncertain

0.014

D;D

Polyphen

0.20

B;B

Vest4

0.28

MutPred

0.64

Loss of solvent accessibility (P = 0.0056);.;

MVP

0.43

MPC

0.49

ClinPred

0.12

GERP RS

1.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.058

gMVP

0.67

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