rs778480216
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_005236.3(ERCC4):c.889T>A(p.Tyr297Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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. Y297C) has been classified as Uncertain significance.
Frequency
Consequence
NM_005236.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ERCC4 | NM_005236.3 | c.889T>A | p.Tyr297Asn | missense_variant | 5/11 | ENST00000311895.8 | |
ERCC4 | XM_011522424.4 | c.1027T>A | p.Tyr343Asn | missense_variant | 6/12 | ||
ERCC4 | XM_047433774.1 | c.100T>A | p.Tyr34Asn | missense_variant | 2/8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ERCC4 | ENST00000311895.8 | c.889T>A | p.Tyr297Asn | missense_variant | 5/11 | 1 | NM_005236.3 | P1 | |
ENST00000570663.1 | n.267A>T | non_coding_transcript_exon_variant | 2/2 | 2 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251294Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135834
GnomAD4 exome Cov.: 29
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
Cockayne syndrome;C0268140:Xeroderma pigmentosum, group F;C3808988:Fanconi anemia complementation group Q Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Nov 04, 2016 | This sequence change replaces tyrosine with asparagine at codon 297 of the ERCC4 protein (p.Tyr297Asn). The tyrosine residue is moderately conserved and there is a large physicochemical difference between tyrosine and asparagine. This variant is present in population databases (rs778480216, ExAC 0.002%) but has not been reported in the literature in individuals with an ERCC4-related disease. In summary, this variant is a rare missense change with uncertain impact on protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. 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 do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at