rs773007457
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_005236.3(ERCC4):c.1633G>A(p.Gly545Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000192 in 1,613,990 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 (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Uncertain significancein ClinVar.
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.1633G>A | p.Gly545Arg | missense_variant | 8/11 | ENST00000311895.8 | |
ERCC4 | XM_011522424.4 | c.1771G>A | p.Gly591Arg | missense_variant | 9/12 | ||
ERCC4 | XM_047433774.1 | c.844G>A | p.Gly282Arg | missense_variant | 5/8 | ||
ERCC4 | XM_011522427.2 | c.283G>A | p.Gly95Arg | missense_variant | 3/6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ERCC4 | ENST00000311895.8 | c.1633G>A | p.Gly545Arg | missense_variant | 8/11 | 1 | NM_005236.3 | P1 | |
ENST00000570663.1 | n.71C>T | non_coding_transcript_exon_variant | 1/2 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000592 AC: 9AN: 152098Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000199 AC: 5AN: 251376Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135876
GnomAD4 exome AF: 0.0000150 AC: 22AN: 1461892Hom.: 0 Cov.: 32 AF XY: 0.0000165 AC XY: 12AN XY: 727248
GnomAD4 genome ? AF: 0.0000592 AC: 9AN: 152098Hom.: 0 Cov.: 32 AF XY: 0.0000808 AC XY: 6AN XY: 74292
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 | Jun 02, 2022 | This variant has not been reported in the literature in individuals affected with ERCC4-related conditions. 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 sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 541249). This variant is present in population databases (rs773007457, gnomAD 0.02%). This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 545 of the ERCC4 protein (p.Gly545Arg). - |
Xeroderma pigmentosum Uncertain:1
Uncertain significance, criteria provided, single submitter | curation | Sema4, Sema4 | Jan 04, 2022 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at