chr16-13920206-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_005236.3(ERCC4):c.41C>T(p.Pro14Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000871 in 1,607,238 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign 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. P14R) 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 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ERCC4 | NM_005236.3 | c.41C>T | p.Pro14Leu | missense_variant | 1/11 | ENST00000311895.8 | |
LOC105371093 | XR_007065000.1 | n.82+6319G>A | intron_variant, non_coding_transcript_variant | ||||
ERCC4 | XM_011522424.4 | c.41C>T | p.Pro14Leu | missense_variant | 1/12 | ||
LOC105371093 | XR_007064999.1 | n.82+6319G>A | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ERCC4 | ENST00000311895.8 | c.41C>T | p.Pro14Leu | missense_variant | 1/11 | 1 | NM_005236.3 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152238Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000286 AC: 7AN: 244384Hom.: 0 AF XY: 0.0000300 AC XY: 4AN XY: 133124
GnomAD4 exome AF: 0.00000893 AC: 13AN: 1455000Hom.: 0 Cov.: 35 AF XY: 0.00000967 AC XY: 7AN XY: 724174
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152238Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74388
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 | Mar 22, 2019 | 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: "Possibly Damaging"; Align-GVGD: "Class C0"). 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. This variant is present in population databases (rs754622238, ExAC 0.05%) but has not been reported in the literature in individuals with a ERCC4-related disease. This sequence change replaces proline with leucine at codon 14 of the ERCC4 protein (p.Pro14Leu). The proline residue is moderately conserved and there is a moderate physicochemical difference between proline and leucine. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at