Genetic Variant NM_030649.3:c.1988T>C (chr1-1294553-A-G) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_030649.3(ACAP3):c.1988T>C(p.Val663Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000147 in 1,500,730 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

ACAP3
NM_030649.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.21

Publications

0 publications found

Variant links:

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]

ACAP3 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.031737983).

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.1988T>C	p.Val663Ala	missense	Exon 21 of 24	NP_085152.2	Q96P50-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ACAP3	ENST00000354700.10	TSL:1 MANE Select	c.1988T>C	p.Val663Ala	missense	Exon 21 of 24	ENSP00000346733.5	Q96P50-3
ACAP3	ENST00000353662.4	TSL:1	c.1763T>C	p.Val588Ala	missense	Exon 18 of 21	ENSP00000321139.4	Q96P50-1
ACAP3	ENST00000467278.5	TSL:1	n.1514T>C		non_coding_transcript_exon	Exon 11 of 14

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152062

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000312

AC:

AN:

96154

AF XY:

0.0000366

show subpopulations

Gnomad AFR exome

AF:

0.00

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

AF:

0.0000141

AC:

AN:

1348668

Hom.:

Cov.:

AF XY:

0.0000165

AC XY:

AN XY:

665752

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

27802

American (AMR)

AF:

0.00

AC:

AN:

26492

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23248

East Asian (EAS)

AF:

0.00

AC:

AN:

32852

South Asian (SAS)

AF:

0.000230

AC:

AN:

73818

European-Finnish (FIN)

AF:

0.00

AC:

AN:

37114

Middle Eastern (MID)

AF:

0.000202

AC:

AN:

4962

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1066344

Other (OTH)

AF:

0.0000178

AC:

AN:

56036

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.412

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152062

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74290

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41426

American (AMR)

AF:

0.00

AC:

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.000621

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10596

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67974

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000380

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.085

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.59

CADD

Benign

(source)

DANN

Benign

0.51

DEOGEN2

Benign

0.040

Eigen

Benign

-0.84

Eigen_PC

Benign

-0.79

FATHMM_MKL

Benign

0.24

LIST_S2

Benign

0.76

M_CAP

Benign

0.023

MetaRNN

Benign

0.032

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

PhyloP100

1.2

PrimateAI

Pathogenic

0.91

PROVEAN

Benign

-0.74

REVEL

Benign

0.031

Sift

Benign

0.50

Sift4G

Benign

0.51

Polyphen

0.010

Vest4

0.27

MutPred

0.32

Loss of stability (P = 0.0241)

MVP

0.081

MPC

0.47

ClinPred

0.020

GERP RS

2.6

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.7

Varity_R

0.061

gMVP

0.18

Mutation Taster

=95/5

polymorphism

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over