1-1294493-G-T

Variant names:

• chr1-1294493-G-T
• rs776871542
• NM_030649.3:c.2048C>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_030649.3(ACAP3):​c.2048C>A​(p.Ala683Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000216 in 1,389,428 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A683V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000022 (0 hom.)
• Consequence: ACAP3 NM_030649.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.89
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030649.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACAP3	NM_030649.3	MANE Select	c.2048C>A	p.Ala683Glu	missense	Exon 21 of 24	NP_085152.2	Q96P50-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACAP3	ENST00000354700.10	TSL:1 MANE Select	c.2048C>A	p.Ala683Glu	missense	Exon 21 of 24	ENSP00000346733.5	Q96P50-3
	ACAP3	ENST00000353662.4	TSL:1	c.1823C>A	p.Ala608Glu	missense	Exon 18 of 21	ENSP00000321139.4	Q96P50-1
	ACAP3	ENST00000467278.5	TSL:1	n.1574C>A		non_coding_transcript_exon	Exon 11 of 14

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000216 AC: 3 AN: 1389428 Hom.: 0 Cov.: 32 AF XY: 0.00000145 AC XY: 1 AN XY: 687540

African (AFR) AF: 0.00 AC: 0 AN: 30038

American (AMR) AF: 0.00 AC: 0 AN: 36368

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24566

East Asian (EAS) AF: 0.00 AC: 0 AN: 35640

South Asian (SAS) AF: 0.00 AC: 0 AN: 79440

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37310

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5656

European-Non Finnish (NFE) AF: 0.00000277 AC: 3 AN: 1082830

Other (OTH) AF: 0.00 AC: 0 AN: 57580

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Uncertain	0.053	T
BayesDel_noAF	Benign	-0.16
CADD	Uncertain	23
DANN	Benign	0.97
DEOGEN2	Benign	0.066	T
Eigen	Benign	-0.13
Eigen_PC	Benign	-0.20
FATHMM_MKL	Benign	0.57	D
LIST_S2	Benign	0.81	T
M_CAP	Pathogenic	0.44	D
MetaRNN	Uncertain	0.71	D
MetaSVM	Benign	-0.87	T
MutationAssessor	Benign	1.6	L
PhyloP100		1.9
PrimateAI	Pathogenic	0.79	T
PROVEAN	Benign	-1.7	N
REVEL	Uncertain	0.36
Sift	Benign	0.33	T
Sift4G	Benign	0.68	T
Polyphen		0.92	P
Vest4		0.55
MutPred		0.52		Gain of disorder (P = 0.0565)
MVP		0.63
MPC		0.75
ClinPred		0.54	D
GERP RS		3.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.12
gMVP		0.66
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs776871542; hg19: chr1-1229873;