rs148791570
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6
The NM_005236.3(ERCC4):c.325G>A(p.Ala109Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000177 in 1,613,246 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 Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A109V) has been classified as Uncertain significance.
Frequency
Consequence
NM_005236.3 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ERCC4 | NM_005236.3 | c.325G>A | p.Ala109Thr | missense_variant | 2/11 | ENST00000311895.8 | |
LOC105371093 | XR_007065000.1 | n.82+4377C>T | intron_variant, non_coding_transcript_variant | ||||
ERCC4 | XM_011522424.4 | c.325G>A | p.Ala109Thr | missense_variant | 2/12 | ||
LOC105371093 | XR_007064999.1 | n.82+4377C>T | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ERCC4 | ENST00000311895.8 | c.325G>A | p.Ala109Thr | missense_variant | 2/11 | 1 | NM_005236.3 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000959 AC: 146AN: 152164Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000267 AC: 67AN: 251316Hom.: 0 AF XY: 0.000191 AC XY: 26AN XY: 135856
GnomAD4 exome AF: 0.0000958 AC: 140AN: 1460964Hom.: 0 Cov.: 30 AF XY: 0.0000922 AC XY: 67AN XY: 726846
GnomAD4 genome AF: 0.000959 AC: 146AN: 152282Hom.: 0 Cov.: 32 AF XY: 0.000859 AC XY: 64AN XY: 74464
ClinVar
Submissions by phenotype
Xeroderma pigmentosum Uncertain:1
Uncertain significance, criteria provided, single submitter | curation | Sema4, Sema4 | Aug 13, 2021 | - - |
Xeroderma pigmentosum, group F Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Dec 22, 2020 | - - |
Cockayne syndrome;C0268140:Xeroderma pigmentosum, group F;C3808988:Fanconi anemia complementation group Q Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Dec 26, 2023 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Feb 22, 2021 | This variant is associated with the following publications: (PMID: 28767289) - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at