17-27309188-A-G

Position:

• chr17-27309188-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_015626.10(WSB1):​c.800A>G​(p.Asp267Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: WSB1 NM_015626.10 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.28

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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.843

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WSB1	NM_015626.10	c.800A>G	p.Asp267Gly	missense_variant	6/9	ENST00000262394.7	NP_056441.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WSB1	ENST00000262394.7	c.800A>G	p.Asp267Gly	missense_variant	6/9	1	NM_015626.10	ENSP00000262394.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

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

Feb 09, 2023

The c.800A>G (p.D267G) alteration is located in exon 6 (coding exon 6) of the WSB1 gene. This alteration results from a A to G substitution at nucleotide position 800, causing the aspartic acid (D) at amino acid position 267 to be replaced by a glycine (G). 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	0.94
BayesDel_addAF	Pathogenic	0.33	D
BayesDel_noAF	Pathogenic	0.23
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.24	T;.;T
Eigen	Pathogenic	0.89
Eigen_PC	Pathogenic	0.87
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.96	D;D;D
M_CAP	Uncertain	0.13	D
MetaRNN	Pathogenic	0.84	D;D;D
MetaSVM	Uncertain	0.19	D
MutationAssessor	Uncertain	2.3	M;.;.
PrimateAI	Uncertain	0.73	T
PROVEAN	Pathogenic	-6.4	D;D;.
REVEL	Pathogenic	0.72
Sift	Benign	0.034	D;D;.
Sift4G	Uncertain	0.0090	D;D;D
Polyphen		0.99	D;D;.
Vest4		0.90
MutPred		0.64		Loss of sheet (P = 0.1158);.;.;
MVP		0.59
MPC		0.37
ClinPred		0.99	D
GERP RS		5.8
RBP_binding_hub_radar		0.97
RBP_regulation_power_radar		2.7
Varity_R		0.54
gMVP		0.64

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-25636214;