rs201894064
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM1BP4_Moderate
The NM_000124.4(ERCC6):c.1835G>A(p.Arg612Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000551 in 1,613,978 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 (★★).
Frequency
Consequence
NM_000124.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ERCC6 | NM_000124.4 | c.1835G>A | p.Arg612Gln | missense_variant | 9/21 | ENST00000355832.10 | |
ERCC6 | NM_001346440.2 | c.1835G>A | p.Arg612Gln | missense_variant | 9/21 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ERCC6 | ENST00000355832.10 | c.1835G>A | p.Arg612Gln | missense_variant | 9/21 | 1 | NM_000124.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000723 AC: 11AN: 152158Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000637 AC: 16AN: 251258Hom.: 0 AF XY: 0.000103 AC XY: 14AN XY: 135796
GnomAD4 exome AF: 0.0000534 AC: 78AN: 1461702Hom.: 0 Cov.: 33 AF XY: 0.0000688 AC XY: 50AN XY: 727166
GnomAD4 genome ? AF: 0.0000722 AC: 11AN: 152276Hom.: 0 Cov.: 32 AF XY: 0.0000672 AC XY: 5AN XY: 74458
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Claritas Genomics | Oct 22, 2013 | - - |
Cerebrooculofacioskeletal syndrome 1;C0265201:DE SANCTIS-CACCHIONE SYNDROME;C0751038:Cockayne syndrome type 2 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Counsyl | Aug 24, 2017 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 01, 2022 | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 612 of the ERCC6 protein (p.Arg612Gln). This variant is present in population databases (rs201894064, gnomAD 0.04%). This variant has not been reported in the literature in individuals affected with ERCC6-related conditions. ClinVar contains an entry for this variant (Variation ID: 190154). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C35". The glutamine 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