Genetic Variant ACAP3:p.Gly659Ser (chr1-1294566-C-T) – 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.1975G>A(p.Gly659Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000132 in 1,507,824 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000072 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00014 ( 0 hom. )

Consequence

ACAP3
NM_030649.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.44

Publications

1 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=0.05347988).

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.1975G>A	p.Gly659Ser	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.1975G>A	p.Gly659Ser	missense	Exon 21 of 24	ENSP00000346733.5	Q96P50-3
ACAP3	ENST00000353662.4	TSL:1	c.1750G>A	p.Gly584Ser	missense	Exon 18 of 21	ENSP00000321139.4	Q96P50-1
ACAP3	ENST00000467278.5	TSL:1	n.1501G>A		non_coding_transcript_exon	Exon 11 of 14

Frequencies

GnomAD3 genomes

AF:

0.0000723

AC:

AN:

152132

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:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000162

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000382

AC:

AN:

104628

AF XY:

0.0000679

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:

0.0000960

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000139

AC:

188

AN:

1355578

Hom.:

Cov.:

AF XY:

0.000115

AC XY:

AN XY:

669152

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

28534

American (AMR)

AF:

0.00

AC:

AN:

27712

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23380

East Asian (EAS)

AF:

0.00

AC:

AN:

33524

South Asian (SAS)

AF:

0.00

AC:

AN:

74376

European-Finnish (FIN)

AF:

0.00

AC:

AN:

38406

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5008

European-Non Finnish (NFE)

AF:

0.000168

AC:

179

AN:

1068380

Other (OTH)

AF:

0.000160

AC:

AN:

56258

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

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:

0.0000723

AC:

AN:

152246

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74444

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41558

American (AMR)

AF:

0.00

AC:

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5166

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000162

AC:

AN:

67990

Other (OTH)

AF:

0.00

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.530

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:

0.0000804

Hom.:

Bravo

AF:

0.0000756

ExAC

AF:

0.0000367

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

0.089

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.66

CADD

Benign

(source)

DANN

Benign

0.88

DEOGEN2

Benign

0.022

Eigen

Benign

-0.82

Eigen_PC

Benign

-0.71

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.72

M_CAP

Benign

0.016

MetaRNN

Benign

0.053

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.34

PhyloP100

4.4

PrimateAI

Uncertain

0.73

PROVEAN

Benign

0.050

REVEL

Benign

0.072

Sift

Benign

0.76

Sift4G

Benign

0.40

Polyphen

0.0

Vest4

0.23

MutPred

0.34

Gain of helix (P = 0.0325)

MVP

0.081

MPC

0.38

ClinPred

0.040

GERP RS

-0.16

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.7

Varity_R

0.055

gMVP

0.27

Mutation Taster

=94/6

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

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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