Variant chr17-27294423-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_015626.10(WSB1):c.28G>A(p.Glu10Lys) variant causes a missense change. The variant allele was found at a frequency of 0.0000347 in 1,613,692 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 0.00011 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000027 ( 0 hom. )

Consequence

WSB1
NM_015626.10 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.21

Variant links:

Genes affected

WSB1 (HGNC:19221): (WD repeat and SOCS box containing 1) This gene encodes a member of the WD-protein subfamily. This protein shares a high sequence identity to mouse and chick proteins. It contains several WD-repeats spanning most of the protein and an SOCS box in the C-terminus. Alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

WSB1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.21018183).

BS2

High AC in GnomAd4 at 16 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WSB1	NM_015626.10 linkuse as main transcript	c.28G>A	p.Glu10Lys	missense_variant	1/9	ENST00000262394.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WSB1	ENST00000262394.7 linkuse as main transcript	c.28G>A	p.Glu10Lys	missense_variant	1/9	1	NM_015626.10	P1	Q9Y6I7-1

Frequencies

GnomAD3 genomes

AF:

0.000105

AC:

AN:

152190

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000217

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

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:

0.000956

GnomAD3 exomes

AF:

0.0000643

AC:

AN:

248788

Hom.:

AF XY:

0.0000668

AC XY:

AN XY:

134688

show subpopulations

Gnomad AFR exome

AF:

0.000246

Gnomad AMR exome

AF:

0.000174

Gnomad ASJ exome

AF:

0.0000993

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000654

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000269

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000274

AC:

AN:

1461502

Hom.:

Cov.:

AF XY:

0.0000344

AC XY:

AN XY:

727040

show subpopulations

Gnomad4 AFR exome

AF:

0.000179

Gnomad4 AMR exome

AF:

0.000157

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000180

Gnomad4 OTH exome

AF:

0.0000663

GnomAD4 genome

AF:

0.000105

AC:

AN:

152190

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

74346

show subpopulations

Gnomad4 AFR

AF:

0.000217

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.000956

Bravo

AF:

0.000121

ExAC

AF:

0.0000659

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 09, 2021

The c.28G>A (p.E10K) alteration is located in exon 1 (coding exon 1) of the WSB1 gene. This alteration results from a G to A substitution at nucleotide position 28, causing the glutamic acid (E) at amino acid position 10 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.59

BayesDel_addAF

Benign

-0.0034

BayesDel_noAF

Uncertain

0.050

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.042

.;T;.;T;.;T;T;.;T

Eigen

Uncertain

0.25

Eigen_PC

Uncertain

0.36

FATHMM_MKL

Benign

0.66

LIST_S2

Uncertain

0.89

D;D;D;T;T;D;T;T;T

M_CAP

Benign

0.028

MetaRNN

Benign

0.21

T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.77

MutationAssessor

Benign

1.5

.;L;.;.;.;.;.;L;.

MutationTaster

Benign

1.0

D;D;D;N;N;N

PrimateAI

Pathogenic

0.88

PROVEAN

Benign

-0.59

.;N;.;.;.;.;N;N;.

REVEL

Benign

0.19

Sift

Benign

0.054

.;T;.;.;.;.;D;D;.

Sift4G

Benign

0.076

T;T;D;D;.;T;D;T;D

Polyphen

0.0020, 0.0040, 1.0, 0.99

.;B;.;.;.;B;D;D;.

Vest4

0.37, 0.68, 0.56, 0.67, 0.66, 0.70

MutPred

0.49

Gain of MoRF binding (P = 9e-04);Gain of MoRF binding (P = 9e-04);Gain of MoRF binding (P = 9e-04);Gain of MoRF binding (P = 9e-04);Gain of MoRF binding (P = 9e-04);Gain of MoRF binding (P = 9e-04);Gain of MoRF binding (P = 9e-04);Gain of MoRF binding (P = 9e-04);Gain of MoRF binding (P = 9e-04);

MVP

0.55

MPC

0.12

ClinPred

0.17

GERP RS

5.3

Varity_R

0.30

gMVP

0.70

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over