2-127292731-T-C
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The ENST00000285398.7(ERCC3):āc.350A>Gā(p.Lys117Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000427 in 1,614,114 control chromosomes in the GnomAD database, including 1 homozygotes. 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 (ā ā ). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. K117N) has been classified as Uncertain significance.
Frequency
Consequence
ENST00000285398.7 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 | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ERCC3 | NM_000122.2 | c.350A>G | p.Lys117Arg | missense_variant | 3/15 | ENST00000285398.7 | NP_000113.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ERCC3 | ENST00000285398.7 | c.350A>G | p.Lys117Arg | missense_variant | 3/15 | 1 | NM_000122.2 | ENSP00000285398 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000394 AC: 6AN: 152214Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000318 AC: 8AN: 251400Hom.: 0 AF XY: 0.0000368 AC XY: 5AN XY: 135880
GnomAD4 exome AF: 0.0000431 AC: 63AN: 1461782Hom.: 1 Cov.: 33 AF XY: 0.0000509 AC XY: 37AN XY: 727202
GnomAD4 genome AF: 0.0000394 AC: 6AN: 152332Hom.: 0 Cov.: 33 AF XY: 0.0000403 AC XY: 3AN XY: 74496
ClinVar
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Dec 10, 2023 | This sequence change replaces lysine, which is basic and polar, with arginine, which is basic and polar, at codon 117 of the ERCC3 protein (p.Lys117Arg). This variant is present in population databases (rs1805161, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with ERCC3-related conditions. ClinVar contains an entry for this variant (Variation ID: 134126). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt ERCC3 protein function with a negative predictive value of 80%. 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. - |
not specified Other:1
not provided, no classification provided | reference population | ITMI | Sep 19, 2013 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at