Genetic Variant ASAP3:p.Val846Ile (chr1-23431706-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_017707.4(ASAP3):c.2536G>A(p.Val846Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000158 in 1,523,480 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V846F) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 30)

Exomes 𝑓: 0.00017 ( 0 hom. )

Consequence

ASAP3
NM_017707.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.61

Publications

2 publications found

Variant links:

Genes affected

ASAP3 (HGNC:14987): (ArfGAP with SH3 domain, ankyrin repeat and PH domain 3) This gene encodes a member of a subfamily of ADP-ribosylation factor(Arf) GTPase-activating proteins that contain additional ankyrin repeat and pleckstrin homology domains. The Arf GAP domain of this protein catalyzes the hydrolysis of GTP bound to Arf proteins. The encoded protein promotes cell differentiation and migration and has been implicated in cancer cell invasion. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2009]

ASAP3 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=0.067222774).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017707.4. 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
	ASAP3	NM_017707.4	MANE Select	c.2536G>A	p.Val846Ile	missense	Exon 23 of 25	NP_060177.2
	ASAP3	NM_001143778.2		c.2509G>A	p.Val837Ile	missense	Exon 22 of 24	NP_001137250.1	Q8TDY4-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ASAP3	ENST00000336689.8	TSL:1 MANE Select	c.2536G>A	p.Val846Ile	missense	Exon 23 of 25	ENSP00000338769.3	Q8TDY4-1
ASAP3	ENST00000948796.1		c.2605G>A	p.Val869Ile	missense	Exon 23 of 25	ENSP00000618855.1
ASAP3	ENST00000857995.1		c.2599G>A	p.Val867Ile	missense	Exon 23 of 25	ENSP00000528054.1

Frequencies

GnomAD3 genomes

AF:

0.0000592

AC:

AN:

152066

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000578

AC:

AN:

172920

AF XY:

0.0000766

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000501

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000579

Gnomad NFE exome

AF:

0.0000711

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000168

AC:

231

AN:

1371296

Hom.:

Cov.:

AF XY:

0.000169

AC XY:

114

AN XY:

674878

show subpopulations

African (AFR)

AF:

0.0000674

AC:

AN:

29670

American (AMR)

AF:

0.00

AC:

AN:

28324

Ashkenazi Jewish (ASJ)

AF:

0.0000495

AC:

AN:

20198

East Asian (EAS)

AF:

0.0000262

AC:

AN:

38108

South Asian (SAS)

AF:

0.0000852

AC:

AN:

70462

European-Finnish (FIN)

AF:

0.0000199

AC:

AN:

50246

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3922

European-Non Finnish (NFE)

AF:

0.000197

AC:

212

AN:

1074106

Other (OTH)

AF:

0.000142

AC:

AN:

56260

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

100

<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:

0.0000591

AC:

AN:

152184

Hom.:

Cov.:

AF XY:

0.0000672

AC XY:

AN XY:

74382

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41514

American (AMR)

AF:

0.0000654

AC:

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.000193

AC:

AN:

5178

South Asian (SAS)

AF:

0.00

AC:

AN:

4806

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10594

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000882

AC:

AN:

68022

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

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:

0.0000658

Hom.:

Bravo

AF:

0.0000567

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000519

AC:

ExAC

AF:

0.0000497

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

0.096

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.46

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.026

Eigen

Benign

-0.37

Eigen_PC

Benign

-0.28

FATHMM_MKL

Benign

0.40

M_CAP

Benign

0.024

MetaRNN

Benign

0.067

MetaSVM

Benign

-1.0

MutationAssessor

Benign

2.0

PhyloP100

1.6

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-0.45

REVEL

Benign

0.021

Sift

Uncertain

0.0050

Sift4G

Pathogenic

0.0

Polyphen

0.10

Vest4

0.22

MutPred

0.19

Loss of loop (P = 0.1242)

MVP

0.34

MPC

0.23

ClinPred

0.096

GERP RS

3.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.051

gMVP

0.13

Mutation Taster

=87/13

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