chr16-13920173-C-T
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_005236.3(ERCC4):c.8C>T(p.Ser3Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000748 in 1,605,214 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. S3S) has been classified as Likely benign.
Frequency
Consequence
NM_005236.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ERCC4 | NM_005236.3 | c.8C>T | p.Ser3Leu | missense_variant | 1/11 | ENST00000311895.8 | |
LOC105371093 | XR_007065000.1 | n.82+6352G>A | intron_variant, non_coding_transcript_variant | ||||
ERCC4 | XM_011522424.4 | c.8C>T | p.Ser3Leu | missense_variant | 1/12 | ||
LOC105371093 | XR_007064999.1 | n.82+6352G>A | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ERCC4 | ENST00000311895.8 | c.8C>T | p.Ser3Leu | missense_variant | 1/11 | 1 | NM_005236.3 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000328 AC: 5AN: 152246Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000290 AC: 7AN: 241614Hom.: 0 AF XY: 0.0000303 AC XY: 4AN XY: 132076
GnomAD4 exome AF: 0.0000791 AC: 115AN: 1452968Hom.: 0 Cov.: 35 AF XY: 0.0000719 AC XY: 52AN XY: 723278
GnomAD4 genome AF: 0.0000328 AC: 5AN: 152246Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74376
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 | Labcorp Genetics (formerly Invitae), Labcorp | Jun 03, 2023 | 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. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 291093). This variant has not been reported in the literature in individuals affected with ERCC4-related conditions. This variant is present in population databases (rs148904556, gnomAD 0.006%). This sequence change replaces serine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 3 of the ERCC4 protein (p.Ser3Leu). - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Sep 01, 2016 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at