Genetic Variant ASAP3:p.Arg858Gln (chr1-23431099-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_017707.4(ASAP3):c.2573G>A(p.Arg858Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000216 in 1,572,988 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000020 ( 0 hom. )

Consequence

ASAP3
NM_017707.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.72

Publications

1 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.18138596).

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.2573G>A	p.Arg858Gln	missense	Exon 24 of 25	NP_060177.2
	ASAP3	NM_001143778.2		c.2546G>A	p.Arg849Gln	missense	Exon 23 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.2573G>A	p.Arg858Gln	missense	Exon 24 of 25	ENSP00000338769.3	Q8TDY4-1
ASAP3	ENST00000948796.1		c.2642G>A	p.Arg881Gln	missense	Exon 24 of 25	ENSP00000618855.1
ASAP3	ENST00000857995.1		c.2636G>A	p.Arg879Gln	missense	Exon 24 of 25	ENSP00000528054.1

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152250

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000723

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:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000704

AC:

AN:

184540

AF XY:

0.0000810

show subpopulations

Gnomad AFR exome

AF:

0.0000908

Gnomad AMR exome

AF:

0.000220

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000386

Gnomad OTH exome

AF:

0.000206

GnomAD4 exome

AF:

0.0000197

AC:

AN:

1420738

Hom.:

Cov.:

AF XY:

0.0000256

AC XY:

AN XY:

702974

show subpopulations

African (AFR)

AF:

0.0000306

AC:

AN:

32708

American (AMR)

AF:

0.000183

AC:

AN:

38232

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25378

East Asian (EAS)

AF:

0.00

AC:

AN:

37680

South Asian (SAS)

AF:

0.0000371

AC:

AN:

80806

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50020

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5714

European-Non Finnish (NFE)

AF:

0.0000137

AC:

AN:

1091354

Other (OTH)

AF:

0.0000340

AC:

AN:

58846

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

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:

0.0000394

AC:

AN:

152250

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74382

show subpopulations

African (AFR)

AF:

0.0000723

AC:

AN:

41474

American (AMR)

AF:

0.00

AC:

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5198

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

68044

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

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:

0.0000581

Hom.:

Bravo

AF:

0.0000982

ExAC

AF:

0.0000674

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

0.28

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.22

CADD

Uncertain

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.021

Eigen

Uncertain

0.50

Eigen_PC

Uncertain

0.52

FATHMM_MKL

Uncertain

0.95

M_CAP

Benign

0.023

MetaRNN

Benign

0.18

MetaSVM

Benign

-0.78

MutationAssessor

Uncertain

2.0

PhyloP100

2.7

PrimateAI

Benign

0.46

PROVEAN

Benign

-1.5

REVEL

Benign

0.22

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.47

MVP

0.76

MPC

0.30

ClinPred

0.60

GERP RS

4.9

Varity_R

0.27

gMVP

0.38

Mutation Taster

=79/21

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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