chr17-27306848-C-G

Position:

• chr17-27306848-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_015626.10(WSB1):​c.677C>G​(p.Ser226Cys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: WSB1 NM_015626.10 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.14

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WSB1	NM_015626.10	c.677C>G	p.Ser226Cys	missense_variant	5/9	ENST00000262394.7	NP_056441.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WSB1	ENST00000262394.7	c.677C>G	p.Ser226Cys	missense_variant	5/9	1	NM_015626.10	ENSP00000262394.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 14, 2024

The c.677C>G (p.S226C) alteration is located in exon 5 (coding exon 5) of the WSB1 gene. This alteration results from a C to G substitution at nucleotide position 677, causing the serine (S) at amino acid position 226 to be replaced by a cysteine (C). 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	Benign	0.20
BayesDel_addAF	Benign	0.0073	T
BayesDel_noAF	Benign	-0.23
CADD	Benign	21
DANN	Benign	0.22
DEOGEN2	Benign	0.054	T;T;.;T;T;.;T
Eigen	Benign	-0.025
Eigen_PC	Benign	0.13
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.71	T;T;D;T;T;T;T
M_CAP	Benign	0.038	D
MetaRNN	Uncertain	0.45	T;T;T;T;T;T;T
MetaSVM	Benign	-0.81	T
MutationAssessor	Benign	1.5	L;.;.;.;.;.;.
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	0.79	N;.;.;.;N;N;.
REVEL	Benign	0.19
Sift	Benign	0.93	T;.;.;.;T;T;.
Sift4G	Benign	0.37	T;T;T;T;T;T;T
Polyphen		0.0010	B;.;.;B;B;B;.
Vest4		0.41
MutPred		0.76		Loss of disorder (P = 0.0132);.;.;Loss of disorder (P = 0.0132);.;.;.;
MVP		0.068
MPC		0.11
ClinPred		0.75	D
GERP RS		4.4
RBP_binding_hub_radar		0.97
RBP_regulation_power_radar		2.1
Varity_R		0.060
gMVP		0.58

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-25633874; COSMIC: COSV99286265; COSMIC: COSV99286265;