NM_012287.6:c.1025A>C

Variant names:

• chr3-195306602-T-G
• rs1728436455
• NM_012287.6:c.1025A>C

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_012287.6(ACAP2):​c.1025A>C​(p.Gln342Pro) variant causes a missense 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. 13/22 in silico tools predict a damaging outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ACAP2 NM_012287.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.02
• Publications: 0 publications found

Genes affected

ACAP2 (HGNC:16469): (ArfGAP with coiled-coil, ankyrin repeat and PH domains 2) Enables GTPase activator activity. Acts upstream of or within actin filament-based process. Located in ruffle. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000295476 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.934

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012287.6. 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
	ACAP2	NM_012287.6	MANE Select	c.1025A>C	p.Gln342Pro	missense	Exon 13 of 23	NP_036419.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACAP2	ENST00000326793.11	TSL:1 MANE Select	c.1025A>C	p.Gln342Pro	missense	Exon 13 of 23	ENSP00000324287.6	Q15057
	ACAP2	ENST00000867120.1		c.1109A>C	p.Gln370Pro	missense	Exon 14 of 25	ENSP00000537179.1
	ACAP2	ENST00000867114.1		c.1025A>C	p.Gln342Pro	missense	Exon 13 of 24	ENSP00000537173.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Pathogenic	0.39	D
BayesDel_noAF	Pathogenic	0.32
CADD	Pathogenic	32
DANN	Uncertain	1.0
DEOGEN2	Pathogenic	0.82	D
Eigen	Pathogenic	0.86
Eigen_PC	Pathogenic	0.76
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.99	D
M_CAP	Pathogenic	0.32	D
MetaRNN	Pathogenic	0.93	D
MetaSVM	Uncertain	0.54	D
MutationAssessor	Pathogenic	3.9	H
PhyloP100		8.0
PrimateAI	Pathogenic	0.82	D
PROVEAN	Pathogenic	-5.5	D
REVEL	Pathogenic	0.85
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.89
MutPred		0.79		Loss of MoRF binding (P = 0.0629)
MVP		0.90
MPC		1.8
ClinPred		1.0	D
GERP RS		4.5
Varity_R		0.86
gMVP		0.95
Mutation Taster		=29/71	disease causing

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: rs1728436455; hg19: chr3-195027331;