1-1294611-C-A

Variant names:

• chr1-1294611-C-A
• rs760502036
• NM_030649.3:c.1930G>T

Variant summary

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

The NM_030649.3(ACAP3):​c.1930G>T​(p.Glu644*) variant causes a stop gained change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ACAP3 NM_030649.3 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.83
• 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.1930G>T	p.Glu644*	stop_gained	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.1930G>T	p.Glu644*	stop_gained	Exon 21 of 24	ENSP00000346733.5	Q96P50-3
	ACAP3	ENST00000353662.4	TSL:1	c.1705G>T	p.Glu569*	stop_gained	Exon 18 of 21	ENSP00000321139.4	Q96P50-1
	ACAP3	ENST00000467278.5	TSL:1	n.1456G>T		non_coding_transcript_exon	Exon 11 of 14

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000772 AC: 1 AN: 129594 AF XY: 0.00

Gnomad AFR exome AF: 0.000128

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1376586 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 678450

African (AFR) AF: 0.00 AC: 0 AN: 31054

American (AMR) AF: 0.00 AC: 0 AN: 32136

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23508

East Asian (EAS) AF: 0.00 AC: 0 AN: 36054

South Asian (SAS) AF: 0.00 AC: 0 AN: 76794

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 43310

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5354

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1071316

Other (OTH) AF: 0.00 AC: 0 AN: 57060

GnomAD4 genome Cov.: 33

ExAC AF: 0.00000909 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.60	D
BayesDel_noAF	Pathogenic	0.62
CADD	Pathogenic	42
DANN	Uncertain	0.99
Eigen	Uncertain	0.41
Eigen_PC	Benign	0.17
FATHMM_MKL	Uncertain	0.92	D
PhyloP100		5.8
Vest4		0.33
GERP RS		2.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.2
Mutation Taster		=9/191	disease causing (fs/PTC)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs760502036; hg19: chr1-1229991;