1-1301989-C-A

Variant names:

• chr1-1301989-C-A
• NM_030649.3:c.337G>T
• ACAP3 p.Glu113*

Variant summary

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

The NM_030649.3(ACAP3):​c.337G>T​(p.Glu113*) variant causes a stop gained, splice region change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. 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: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ACAP3 NM_030649.3 stop_gained, splice_region
• Scores: Splicing: ADA: 0.8886
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.40
• 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.337G>T	p.Glu113*	stop_gained splice_region	Exon 5 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.337G>T	p.Glu113*	stop_gained splice_region	Exon 5 of 24	ENSP00000346733.5	Q96P50-3
	ACAP3	ENST00000353662.4	TSL:1	c.211G>T	p.Glu71*	stop_gained splice_region	Exon 3 of 21	ENSP00000321139.4	Q96P50-1
	ACAP3	ENST00000492936.5	TSL:1	n.2076G>T		splice_region non_coding_transcript_exon	Exon 4 of 22

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1417998 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 705190

African (AFR) AF: 0.00 AC: 0 AN: 31332

American (AMR) AF: 0.00 AC: 0 AN: 38718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24856

East Asian (EAS) AF: 0.00 AC: 0 AN: 37274

South Asian (SAS) AF: 0.00 AC: 0 AN: 81958

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51182

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5586

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1088950

Other (OTH) AF: 0.00 AC: 0 AN: 58142

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.55	D
BayesDel_noAF	Pathogenic	0.56
CADD	Pathogenic	43
DANN	Uncertain	1.0
Eigen	Pathogenic	0.86
Eigen_PC	Uncertain	0.66
FATHMM_MKL	Pathogenic	0.97	D
PhyloP100		7.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=13/187	disease causing (fs/PTC)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.89
dbscSNV1_RF	Benign	0.64
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr1-1237369;