2-159279893-C-G

Variant names:

• chr2-159279893-C-G
• rs745416660
• NM_001128212.3:c.451G>C

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001128212.3(WDSUB1):​c.451G>C​(p.Gly151Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: WDSUB1 NM_001128212.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.06
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.823

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDSUB1	NM_001128212.3	MANE Select	c.451G>C	p.Gly151Arg	missense	Exon 3 of 11	NP_001121684.1	Q8N9V3-1
	WDSUB1	NM_001128213.2		c.451G>C	p.Gly151Arg	missense	Exon 3 of 11	NP_001121685.1	Q8N9V3-1
	WDSUB1	NM_001330278.2		c.451G>C	p.Gly151Arg	missense	Exon 3 of 11	NP_001317207.1	Q8N9V3-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDSUB1	ENST00000359774.9	TSL:5 MANE Select	c.451G>C	p.Gly151Arg	missense	Exon 3 of 11	ENSP00000352820.4	Q8N9V3-1
	WDSUB1	ENST00000358147.8	TSL:1	c.451G>C	p.Gly151Arg	missense	Exon 3 of 7	ENSP00000350866.4	Q8N9V3-2
	WDSUB1	ENST00000851154.1		c.451G>C	p.Gly151Arg	missense	Exon 3 of 12	ENSP00000521213.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Pathogenic	0.31	D
BayesDel_noAF	Pathogenic	0.21
CADD	Uncertain	25
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.081	T
Eigen	Pathogenic	0.80
Eigen_PC	Pathogenic	0.75
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.96	D
M_CAP	Uncertain	0.086	D
MetaRNN	Pathogenic	0.82	D
MetaSVM	Uncertain	0.46	D
PhyloP100		3.1
PrimateAI	Uncertain	0.55	T
PROVEAN	Pathogenic	-4.6	D
REVEL	Uncertain	0.39
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.0040	D
Polyphen		1.0	D
Vest4		0.55
MutPred		0.72		Gain of solvent accessibility (P = 0.0584)
MVP		0.89
MPC		0.48
ClinPred		1.0	D
GERP RS		5.9
gMVP		0.69
Mutation Taster		=66/34	polymorphism

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

Other links and lift over

dbSNP: rs745416660; hg19: chr2-160136404;