chr1-1295865-C-T

Position:

• chr1-1295865-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000354700.10(ACAP3):​c.1576G>A​(p.Ala526Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 34)
• Consequence: ACAP3 ENST00000354700.10 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0620

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.055781454).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACAP3	NM_030649.3	c.1576G>A	p.Ala526Thr	missense_variant	18/24	ENST00000354700.10	NP_085152.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACAP3	ENST00000354700.10	c.1576G>A	p.Ala526Thr	missense_variant	18/24	1	NM_030649.3	ENSP00000346733	P1
ACAP3	ENST00000353662.4	c.1450G>A	p.Ala484Thr	missense_variant	16/21	1		ENSP00000321139
ACAP3	ENST00000467278.5	n.1102G>A		non_coding_transcript_exon_variant	8/14	1
ACAP3	ENST00000492936.5	n.3315G>A		non_coding_transcript_exon_variant	17/22	1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 34

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 10, 2022

The c.1576G>A (p.A526T) alteration is located in exon 18 (coding exon 18) of the ACAP3 gene. This alteration results from a G to A substitution at nucleotide position 1576, causing the alanine (A) at amino acid position 526 to be replaced by a threonine (T). 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	0.072
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	0.50
DANN	Benign	0.93
DEOGEN2	Benign	0.027	T;.
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.076	N
LIST_S2	Benign	0.56	T;T
M_CAP	Benign	0.0096	T
MetaRNN	Benign	0.056	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.1	M;.
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-0.59	N;N
REVEL	Benign	0.033
Sift	Benign	0.29	T;T
Sift4G	Benign	0.45	T;T
Polyphen		0.0	B;B
Vest4		0.079
MutPred		0.24		Gain of phosphorylation at A526 (P = 0.0337);.;
MVP		0.030
MPC		0.37
ClinPred		0.18	T
GERP RS		1.7
Varity_R		0.030
gMVP		0.22

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-1231245;