21-42850120-G-A
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2BP4_ModerateBS1_Supporting
The NM_018669.6(WDR4):c.1168C>T(p.Arg390Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000285 in 1,613,948 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. 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. R390Q) has been classified as Likely benign.
Frequency
Consequence
NM_018669.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
WDR4 | NM_018669.6 | c.1168C>T | p.Arg390Trp | missense_variant | 11/11 | ENST00000398208.3 | NP_061139.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
WDR4 | ENST00000398208.3 | c.1168C>T | p.Arg390Trp | missense_variant | 11/11 | 1 | NM_018669.6 | ENSP00000381266.2 | ||
WDR4 | ENST00000330317.6 | c.1168C>T | p.Arg390Trp | missense_variant | 11/12 | 1 | ENSP00000328671.2 | |||
WDR4 | ENST00000476326.5 | n.1083C>T | non_coding_transcript_exon_variant | 11/11 | 1 | |||||
WDR4 | ENST00000492742.5 | n.1311C>T | non_coding_transcript_exon_variant | 11/11 | 2 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152250Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000518 AC: 13AN: 251206Hom.: 0 AF XY: 0.0000589 AC XY: 8AN XY: 135824
GnomAD4 exome AF: 0.0000301 AC: 44AN: 1461698Hom.: 0 Cov.: 32 AF XY: 0.0000358 AC XY: 26AN XY: 727164
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152250Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74386
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | May 25, 2022 | The c.1168C>T (p.R390W) alteration is located in exon 11 (coding exon 11) of the WDR4 gene. This alteration results from a C to T substitution at nucleotide position 1168, causing the arginine (R) at amino acid position 390 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jun 08, 2022 | 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals affected with WDR4-related conditions. This variant is present in population databases (rs375403604, gnomAD 0.02%). This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 390 of the WDR4 protein (p.Arg390Trp). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at