Genetic Variant WDSUB1:p.Arg319Thr (chr2-159256372-C-G) – 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_001128212.3(WDSUB1):c.956G>C(p.Arg319Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000436 in 1,604,810 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000098 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000038 ( 0 hom. )

Consequence

WDSUB1
NM_001128212.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.257

Publications

0 publications found

Variant links:

Genes affected

WDSUB1 (HGNC:26697): (WD repeat, sterile alpha motif and U-box domain containing 1) Predicted to enable ubiquitin-protein transferase activity. Predicted to be involved in protein ubiquitination. [provided by Alliance of Genome Resources, Apr 2022]

WDSUB1 links:

Genome browser will be placed here

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=0.027985424).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001128212.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
WDSUB1	NM_001128212.3	MANE Select	c.956G>C	p.Arg319Thr	missense	Exon 9 of 11	NP_001121684.1	Q8N9V3-1
WDSUB1	NM_001128213.2		c.956G>C	p.Arg319Thr	missense	Exon 9 of 11	NP_001121685.1	Q8N9V3-1
WDSUB1	NM_001330278.2		c.956G>C	p.Arg319Thr	missense	Exon 9 of 11	NP_001317207.1	Q8N9V3-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
WDSUB1	ENST00000359774.9	TSL:5 MANE Select	c.956G>C	p.Arg319Thr	missense	Exon 9 of 11	ENSP00000352820.4	Q8N9V3-1
WDSUB1	ENST00000358147.8	TSL:1	c.680G>C	p.Arg227Thr	missense	Exon 5 of 7	ENSP00000350866.4	Q8N9V3-2
WDSUB1	ENST00000851154.1		c.956G>C	p.Arg319Thr	missense	Exon 9 of 12	ENSP00000521213.1

Frequencies

GnomAD3 genomes

AF:

0.000105

AC:

AN:

152180

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000654

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:

0.0000441

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.0000539

AC:

AN:

241256

AF XY:

0.0000692

show subpopulations

Gnomad AFR exome

AF:

0.0000629

Gnomad AMR exome

AF:

0.0000948

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000541

Gnomad OTH exome

AF:

0.000339

GnomAD4 exome

AF:

0.0000379

AC:

AN:

1452512

Hom.:

Cov.:

AF XY:

0.0000388

AC XY:

AN XY:

722020

show subpopulations

African (AFR)

AF:

0.0000304

AC:

AN:

32904

American (AMR)

AF:

0.000142

AC:

AN:

42380

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25870

East Asian (EAS)

AF:

0.00

AC:

AN:

39482

South Asian (SAS)

AF:

0.0000120

AC:

AN:

83406

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53374

Middle Eastern (MID)

AF:

0.00104

AC:

AN:

5748

European-Non Finnish (NFE)

AF:

0.0000307

AC:

AN:

1109278

Other (OTH)

AF:

0.000117

AC:

AN:

60070

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

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:

0.0000985

AC:

AN:

152298

Hom.:

Cov.:

AF XY:

0.000107

AC XY:

AN XY:

74468

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41574

American (AMR)

AF:

0.000653

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10606

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

68008

Other (OTH)

AF:

0.000473

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.547

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:

0.000113

Hom.:

Bravo

AF:

0.000174

ExAC

AF:

0.0000330

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

0.084

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.44

CADD

Benign

(source)

DANN

Benign

0.81

DEOGEN2

Benign

0.0071

Eigen

Benign

-0.78

Eigen_PC

Benign

-0.65

FATHMM_MKL

Benign

0.26

LIST_S2

Benign

0.76

M_CAP

Benign

0.010

MetaRNN

Benign

0.028

MetaSVM

Benign

-1.0

PhyloP100

0.26

PrimateAI

Benign

0.26

PROVEAN

Benign

0.20

REVEL

Benign

0.043

Sift

Benign

0.57

Sift4G

Benign

0.60

Polyphen

0.0

Vest4

0.21

MVP

0.39

MPC

0.11

ClinPred

0.016

GERP RS

1.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

gMVP

0.59

Mutation Taster

=94/6

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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