2-159248402-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_001128212.3(WDSUB1):​c.1243G>A​(p.Glu415Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000589 in 1,611,670 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000060 ( 0 hom. )

Consequence

WDSUB1
NM_001128212.3 missense

Scores

6
9
2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.52
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

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, 0.846

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
WDSUB1NM_001128212.3 linkc.1243G>A p.Glu415Lys missense_variant Exon 10 of 11 ENST00000359774.9 NP_001121684.1 Q8N9V3-1D3DPA6

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
WDSUB1ENST00000359774.9 linkc.1243G>A p.Glu415Lys missense_variant Exon 10 of 11 5 NM_001128212.3 ENSP00000352820.4 Q8N9V3-1

Frequencies

GnomAD3 genomes
AF:
0.0000460
AC:
7
AN:
152122
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000724
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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:
0.0000588
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000161
AC:
4
AN:
248890
Hom.:
0
AF XY:
0.0000149
AC XY:
2
AN XY:
134626
show subpopulations
Gnomad AFR exome
AF:
0.0000625
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000266
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000603
AC:
88
AN:
1459548
Hom.:
0
Cov.:
30
AF XY:
0.0000757
AC XY:
55
AN XY:
726118
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000792
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000460
AC:
7
AN:
152122
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74314
show subpopulations
Gnomad4 AFR
AF:
0.0000724
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000588
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000605
Hom.:
0
ESP6500AA
AF:
0.000227
AC:
1
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.0000165
AC:
2

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Dec 16, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1243G>A (p.E415K) alteration is located in exon 10 (coding exon 9) of the WDSUB1 gene. This alteration results from a G to A substitution at nucleotide position 1243, causing the glutamic acid (E) at amino acid position 415 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
Benign
0.26
BayesDel_addAF
Uncertain
0.12
D
BayesDel_noAF
Uncertain
0.12
CADD
Pathogenic
30
DANN
Pathogenic
1.0
Eigen
Pathogenic
0.77
Eigen_PC
Pathogenic
0.72
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Pathogenic
0.99
.;.;.;D
M_CAP
Uncertain
0.089
D
MetaRNN
Pathogenic
0.85
D;D;D;D
MetaSVM
Uncertain
-0.078
T
PrimateAI
Uncertain
0.72
T
PROVEAN
Uncertain
-3.2
D;D;D;D
REVEL
Uncertain
0.42
Sift
Uncertain
0.0070
D;D;D;D
Sift4G
Uncertain
0.0080
D;D;D;D
Vest4
0.88
MVP
0.82
MPC
0.46
ClinPred
0.83
D
GERP RS
5.8
gMVP
0.75

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.

Other links and lift over

dbSNP: rs139687131; hg19: chr2-160104913; API