chr15-84643474-C-T
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_032856.5(WDR73):c.1133G>A(p.Arg378His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000212 in 1,553,860 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R378C) has been classified as Uncertain significance.
Frequency
Consequence
NM_032856.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
WDR73 | NM_032856.5 | c.1133G>A | p.Arg378His | missense_variant | 8/8 | ENST00000434634.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
WDR73 | ENST00000434634.7 | c.1133G>A | p.Arg378His | missense_variant | 8/8 | 1 | NM_032856.5 | P1 | |
ENST00000348993.9 | n.4971C>T | non_coding_transcript_exon_variant | 4/4 | 1 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152076Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000813 AC: 13AN: 159916Hom.: 0 AF XY: 0.0000709 AC XY: 6AN XY: 84636
GnomAD4 exome AF: 0.0000214 AC: 30AN: 1401666Hom.: 0 Cov.: 33 AF XY: 0.0000145 AC XY: 10AN XY: 691668
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152194Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74406
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 18, 2023 | This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 378 of the WDR73 protein (p.Arg378His). This variant is present in population databases (rs375954913, gnomAD 0.1%). This variant has not been reported in the literature in individuals affected with WDR73-related conditions. ClinVar contains an entry for this variant (Variation ID: 1896197). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Not Available". The histidine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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