rs757218535

Variant names:

• chr2-159282733-C-G
• rs757218535
• NM_001128212.3:c.337G>C

Your query was ambiguous. Multiple possible variants found:

• chr2-159282733-C-G
• chr2-159282733-C-T

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_001128212.3(WDSUB1):​c.337G>C​(p.Ala113Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000041 in 1,461,840 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. A113T) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: WDSUB1 NM_001128212.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.30
• Publications: 1 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: Likely_pathogenic. The variant received 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.959

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.337G>C	p.Ala113Pro	missense	Exon 2 of 11	NP_001121684.1	Q8N9V3-1
	WDSUB1	NM_001128213.2		c.337G>C	p.Ala113Pro	missense	Exon 2 of 11	NP_001121685.1	Q8N9V3-1
	WDSUB1	NM_001330278.2		c.337G>C	p.Ala113Pro	missense	Exon 2 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.337G>C	p.Ala113Pro	missense	Exon 2 of 11	ENSP00000352820.4	Q8N9V3-1
	WDSUB1	ENST00000358147.8	TSL:1	c.337G>C	p.Ala113Pro	missense	Exon 2 of 7	ENSP00000350866.4	Q8N9V3-2
	WDSUB1	ENST00000851154.1		c.337G>C	p.Ala113Pro	missense	Exon 2 of 12	ENSP00000521213.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000410 AC: 6 AN: 1461840 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 727212

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000540 AC: 6 AN: 1111966

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.69
BayesDel_addAF	Uncertain	0.043	T
BayesDel_noAF	Benign	-0.18
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.28	T
Eigen	Benign	-0.038
Eigen_PC	Benign	-0.16
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.96	D
M_CAP	Uncertain	0.097	D
MetaRNN	Pathogenic	0.96	D
MetaSVM	Uncertain	0.17	D
PhyloP100		1.3
PrimateAI	Benign	0.28	T
PROVEAN	Uncertain	-3.4	D
REVEL	Uncertain	0.41
Sift	Benign	0.050	D
Sift4G	Uncertain	0.023	D
Polyphen		0.86	P
Vest4		0.66
MutPred		0.86		Gain of glycosylation at T110 (P = 0.0591)
MVP		0.74
MPC		0.30
ClinPred		0.99	D
GERP RS		3.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
gMVP		0.88
Mutation Taster		=80/20	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: rs757218535; hg19: chr2-160139244;