3-195320803-C-A

Variant names:

• chr3-195320803-C-A
• NM_012287.6:c.755G>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_012287.6(ACAP2):​c.755G>T​(p.Ser252Ile) 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: 32)
• Consequence: ACAP2 NM_012287.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.05

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12818846).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACAP2	NM_012287.6	c.755G>T	p.Ser252Ile	missense_variant	Exon 10 of 23	ENST00000326793.11	NP_036419.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACAP2	ENST00000326793.11	c.755G>T	p.Ser252Ile	missense_variant	Exon 10 of 23	1	NM_012287.6	ENSP00000324287.6
ACAP2	ENST00000450200.2	c.755G>T	p.Ser252Ile	missense_variant	Exon 10 of 23	5		ENSP00000412338.2
ACAP2	ENST00000635383.1	c.755G>T	p.Ser252Ile	missense_variant	Exon 10 of 18	5		ENSP00000489156.1
ACAP2	ENST00000439758.3	c.377G>T	p.Ser126Ile	missense_variant	Exon 6 of 10	4		ENSP00000413388.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 04, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.755G>T (p.S252I) alteration is located in exon 10 (coding exon 10) of the ACAP2 gene. This alteration results from a G to T substitution at nucleotide position 755, causing the serine (S) at amino acid position 252 to be replaced by an isoleucine (I). 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	0.12
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Benign	0.040	T;T;.
Eigen	Benign	-0.41
Eigen_PC	Benign	-0.21
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.95	D;D;D
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.13	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L;.;.
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	-1.3	N;.;.
REVEL	Benign	0.048
Sift	Benign	0.44	T;.;.
Sift4G	Benign	0.42	T;T;T
Polyphen		0.047	B;.;.
Vest4		0.26
MutPred		0.36		Gain of glycosylation at S251 (P = 0.0208);.;Gain of glycosylation at S251 (P = 0.0208);
MVP		0.39
MPC		0.78
ClinPred		0.63	D
GERP RS		3.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.13
gMVP		0.74

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr3-195041532;