chr1-23431036-G-T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_StrongBP6

The NM_017707.4(ASAP3):c.2636C>A(p.Pro879Gln) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000282 in 1,578,068 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/24 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P879S) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00080 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00023 ( 0 hom. )

Consequence

ASAP3
NM_017707.4 missense, splice_region

Scores

Splicing: ADA: 0.001068

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: -1.47

Publications

6 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: Likely_benign. The variant received -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0076680183).

BP6

Variant 1-23431036-G-T is Benign according to our data. Variant chr1-23431036-G-T is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 713031.

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.2636C>A	p.Pro879Gln	missense splice_region	Exon 24 of 25	NP_060177.2
	ASAP3	NM_001143778.2		c.2609C>A	p.Pro870Gln	missense splice_region	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.2636C>A	p.Pro879Gln	missense splice_region	Exon 24 of 25	ENSP00000338769.3	Q8TDY4-1
ASAP3	ENST00000948796.1		c.2705C>A	p.Pro902Gln	missense splice_region	Exon 24 of 25	ENSP00000618855.1
ASAP3	ENST00000857995.1		c.2699C>A	p.Pro900Gln	missense splice_region	Exon 24 of 25	ENSP00000528054.1

Frequencies

GnomAD3 genomes

AF:

0.000801

AC:

122

AN:

152218

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00188

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00170

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000162

Gnomad OTH

AF:

0.00287

GnomAD2 exomes

AF:

0.000303

AC:

AN:

201488

AF XY:

0.000315

show subpopulations

Gnomad AFR exome

AF:

0.00144

Gnomad AMR exome

AF:

0.000695

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000638

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000166

Gnomad OTH exome

AF:

0.00121

GnomAD4 exome

AF:

0.000227

AC:

323

AN:

1425732

Hom.:

Cov.:

AF XY:

0.000236

AC XY:

167

AN XY:

706198

show subpopulations

African (AFR)

AF:

0.00172

AC:

AN:

32648

American (AMR)

AF:

0.000991

AC:

AN:

39342

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24154

East Asian (EAS)

AF:

0.00

AC:

AN:

38580

South Asian (SAS)

AF:

0.0000126

AC:

AN:

79488

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51298

Middle Eastern (MID)

AF:

0.00230

AC:

AN:

5646

European-Non Finnish (NFE)

AF:

0.000161

AC:

176

AN:

1095684

Other (OTH)

AF:

0.000645

AC:

AN:

58892

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

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:

0.000801

AC:

122

AN:

152336

Hom.:

Cov.:

AF XY:

0.000738

AC XY:

AN XY:

74488

show subpopulations

African (AFR)

AF:

0.00188

AC:

AN:

41574

American (AMR)

AF:

0.00170

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000162

AC:

AN:

68034

Other (OTH)

AF:

0.00284

AC:

AN:

2116

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:

0.0000206

Hom.:

Bravo

AF:

0.000926

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ExAC

AF:

0.000281

AC:

ClinVar

ClinVar submissions

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.082

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.51

CADD

Benign

7.2

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.15

Eigen

Benign

-0.45

Eigen_PC

Benign

-0.45

FATHMM_MKL

Benign

0.24

M_CAP

Benign

0.015

MetaRNN

Benign

0.0077

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.0

PhyloP100

-1.5

PrimateAI

Benign

0.29

PROVEAN

Uncertain

-2.9

REVEL

Benign

0.049

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.013

Polyphen

0.0070

Vest4

0.34

MVP

0.51

MPC

0.22

ClinPred

0.033

GERP RS

1.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.094

gMVP

0.22

Mutation Taster

=79/21

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0011

dbscSNV1_RF

Benign

0.22

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