2-218893051-T-C
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_025216.3(WNT10A):āc.1034T>Cā(p.Phe345Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000208 in 1,444,002 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 (ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. F345L) has been classified as Uncertain significance.
Frequency
Consequence
NM_025216.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
WNT10A | NM_025216.3 | c.1034T>C | p.Phe345Ser | missense_variant | 4/4 | ENST00000258411.8 | |
WNT10A | XM_011511929.3 | c.938T>C | p.Phe313Ser | missense_variant | 5/5 | ||
WNT10A | XM_011511930.2 | c.654T>C | p.Leu218= | synonymous_variant | 3/3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
WNT10A | ENST00000258411.8 | c.1034T>C | p.Phe345Ser | missense_variant | 4/4 | 1 | NM_025216.3 | P1 | |
WNT10A | ENST00000458582.1 | c.543T>C | p.Leu181= | synonymous_variant | 2/2 | 3 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome AF: 0.00000208 AC: 3AN: 1444002Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 718698
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Odonto-onycho-dermal dysplasia;C1835492:Tooth agenesis, selective, 4 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 03, 2023 | This sequence change replaces phenylalanine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 345 of the WNT10A protein (p.Phe345Ser). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of odontoonychodermal dysplasia (Invitae). ClinVar contains an entry for this variant (Variation ID: 464178). 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 expected to disrupt WNT10A protein function. This variant disrupts the p.Phe345 amino acid residue in WNT10A. Other variant(s) that disrupt this residue have been observed in individuals with WNT10A-related conditions (PMID: 28976000), which suggests that this may be a clinically significant amino acid residue. 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at