12-48966196-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.
The NM_003394.4(WNT10B):c.1069C>T(p.Arg357Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000254 in 1,613,610 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R357Q) has been classified as Uncertain significance.
Frequency
Consequence
NM_003394.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
WNT10B | NM_003394.4 | c.1069C>T | p.Arg357Trp | missense_variant | 5/5 | ENST00000301061.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
WNT10B | ENST00000301061.9 | c.1069C>T | p.Arg357Trp | missense_variant | 5/5 | 1 | NM_003394.4 | P1 | |
WNT10B | ENST00000403957.5 | c.*351C>T | 3_prime_UTR_variant | 6/6 | 5 | ||||
WNT10B | ENST00000407467.5 | c.*351C>T | 3_prime_UTR_variant | 6/6 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000788 AC: 12AN: 152228Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000319 AC: 8AN: 250836Hom.: 0 AF XY: 0.0000369 AC XY: 5AN XY: 135658
GnomAD4 exome AF: 0.0000198 AC: 29AN: 1461382Hom.: 0 Cov.: 30 AF XY: 0.0000234 AC XY: 17AN XY: 727004
GnomAD4 genome ? AF: 0.0000788 AC: 12AN: 152228Hom.: 0 Cov.: 32 AF XY: 0.0000807 AC XY: 6AN XY: 74374
ClinVar
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Nov 24, 2023 | This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 357 of the WNT10B protein (p.Arg357Trp). This variant is present in population databases (rs368571284, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with WNT10B-related conditions. ClinVar contains an entry for this variant (Variation ID: 2442598). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt WNT10B protein function with a negative predictive value of 80%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Mar 27, 2023 | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at