16-13920202-G-T
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_005236.3(ERCC4):c.37G>T(p.Ala13Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000055 in 1,454,834 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. A13T) has been classified as Likely benign.
Frequency
Consequence
NM_005236.3 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 |
---|---|---|---|---|---|---|---|---|
ERCC4 | NM_005236.3 | c.37G>T | p.Ala13Ser | missense_variant | 1/11 | ENST00000311895.8 | NP_005227.1 | |
ERCC4 | XM_011522424.4 | c.37G>T | p.Ala13Ser | missense_variant | 1/12 | XP_011520726.1 | ||
LOC105371093 | XR_007064999.1 | n.82+6323C>A | intron_variant | |||||
LOC105371093 | XR_007065000.1 | n.82+6323C>A | intron_variant |
Ensembl
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 exomes AF: 0.00000410 AC: 1AN: 244108Hom.: 0 AF XY: 0.00000752 AC XY: 1AN XY: 133024
GnomAD4 exome AF: 0.00000550 AC: 8AN: 1454834Hom.: 0 Cov.: 35 AF XY: 0.00000138 AC XY: 1AN XY: 724094
GnomAD4 genome Cov.: 33
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 | Mar 25, 2019 | 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 missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with ERCC4-related conditions. This variant is present in population databases (rs374243778, ExAC 0.02%). This sequence change replaces alanine with serine at codon 13 of the ERCC4 protein (p.Ala13Ser). The alanine residue is moderately conserved and there is a moderate physicochemical difference between alanine and serine. - |
Xeroderma pigmentosum, group F Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | St. Jude Molecular Pathology, St. Jude Children's Research Hospital | Feb 05, 2025 | The ERCC4 c.37G>T (p.Ala13Ser) missense change has a maximum subpopulation frequency of 0.0063% in gnomAD v2.1.1 (https://gnomad.broadinstitute.org). The in silico tool REVEL predicts a benign effect on protein function, but this prediction has not been confirmed by functional studies. This variant has not been reported in individuals with Fanconi anemia or xeroderma pigmentosum. In summary, the evidence currently available is insufficient to determine the clinical significance of this variant. It has therefore been classified as of uncertain significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at