dbSNP rs747142679: WRAP73:p.Ser395Asn (chr1-3631522-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_017818.4(WRAP73):c.1184G>A(p.Ser395Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000559 in 1,610,006 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

WRAP73
NM_017818.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.314

Publications

0 publications found

Variant links:

Genes affected

WRAP73 (HGNC:12759): (WD repeat containing, antisense to TP73) This gene encodes a member of the WD repeat protein family. WD repeats are minimally conserved regions of approximately 40 amino acids typically bracketed by gly-his and trp-asp (GH-WD), which may facilitate formation of heterotrimeric or multiprotein complexes. Members of this family are involved in a variety of cellular processes, including cell cycle progression, signal transduction, apoptosis, and gene regulation. Studies of the related mouse protein suggest that the encoded protein may play a role in the process of ossification. [provided by RefSeq, Mar 2009]

WRAP73 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=0.06903592).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017818.4. 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
	WRAP73	NM_017818.4	MANE Select	c.1184G>A	p.Ser395Asn	missense	Exon 11 of 12	NP_060288.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
WRAP73	ENST00000270708.12	TSL:1 MANE Select	c.1184G>A	p.Ser395Asn	missense	Exon 11 of 12	ENSP00000270708.7	Q9P2S5
WRAP73	ENST00000378322.7	TSL:1	c.1184G>A	p.Ser395Asn	missense	Exon 11 of 11	ENSP00000367573.3	A0A0A0MRV3
WRAP73	ENST00000960493.1		c.1184G>A	p.Ser395Asn	missense	Exon 11 of 12	ENSP00000630552.1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152246

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:

0.0000941

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000124

AC:

AN:

242146

AF XY:

0.00

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:

0.000143

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000549

AC:

AN:

1457760

Hom.:

Cov.:

AF XY:

0.00000414

AC XY:

AN XY:

724916

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33436

American (AMR)

AF:

0.00

AC:

AN:

44362

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26020

East Asian (EAS)

AF:

0.00

AC:

AN:

39618

South Asian (SAS)

AF:

0.00

AC:

AN:

85654

European-Finnish (FIN)

AF:

0.000116

AC:

AN:

51868

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

9.00e-7

AC:

AN:

1110798

Other (OTH)

AF:

0.0000166

AC:

AN:

60242

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.531

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:

0.00000657

AC:

AN:

152246

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74386

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41466

American (AMR)

AF:

0.00

AC:

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5200

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.0000941

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68036

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.725

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000468

Hom.:

ExAC

AF:

0.0000165

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

0.086

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.75

CADD

Benign

(source)

DANN

Benign

0.86

DEOGEN2

Benign

0.0050

Eigen

Benign

-0.20

Eigen_PC

Benign

-0.0040

FATHMM_MKL

Benign

0.70

LIST_S2

Benign

0.78

M_CAP

Benign

0.0031

MetaRNN

Benign

0.069

MetaSVM

Benign

-0.96

MutationAssessor

Benign

1.6

PhyloP100

0.31

PrimateAI

Benign

0.38

PROVEAN

Benign

0.46

REVEL

Benign

0.089

Sift

Benign

0.55

Sift4G

Benign

0.87

Polyphen

0.0

Vest4

0.11

MutPred

0.47

Loss of catalytic residue at S395 (P = 0.1606)

MVP

0.18

MPC

0.18

ClinPred

0.073

GERP RS

5.5

Varity_R

0.086

gMVP

0.42

Mutation Taster

=92/8

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over