16-13948141-C-G
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2BP4_ModerateBP6
The NM_005236.3(ERCC4):āc.2545C>Gā(p.Gln849Glu) variant causes a missense change. The variant allele was found at a frequency of 0.000052 in 1,614,046 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. Q849L) has been classified as Uncertain significance.
Frequency
Consequence
NM_005236.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ERCC4 | NM_005236.3 | c.2545C>G | p.Gln849Glu | missense_variant | 11/11 | ENST00000311895.8 | |
ERCC4 | XM_011522424.4 | c.2683C>G | p.Gln895Glu | missense_variant | 12/12 | ||
ERCC4 | XM_047433774.1 | c.1756C>G | p.Gln586Glu | missense_variant | 8/8 | ||
ERCC4 | XM_011522427.2 | c.1195C>G | p.Gln399Glu | missense_variant | 6/6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ERCC4 | ENST00000311895.8 | c.2545C>G | p.Gln849Glu | missense_variant | 11/11 | 1 | NM_005236.3 | P1 | |
ERCC4 | ENST00000682617.1 | c.2683C>G | p.Gln895Glu | missense_variant | 12/12 | ||||
ERCC4 | ENST00000389138.7 | n.1822C>G | non_coding_transcript_exon_variant | 6/6 | 2 | ||||
ERCC4 | ENST00000683962.1 | c.*2239C>G | 3_prime_UTR_variant, NMD_transcript_variant | 12/12 |
Frequencies
GnomAD3 genomes AF: 0.0000854 AC: 13AN: 152158Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000875 AC: 22AN: 251414Hom.: 1 AF XY: 0.0000442 AC XY: 6AN XY: 135874
GnomAD4 exome AF: 0.0000486 AC: 71AN: 1461888Hom.: 0 Cov.: 33 AF XY: 0.0000440 AC XY: 32AN XY: 727244
GnomAD4 genome AF: 0.0000854 AC: 13AN: 152158Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74330
ClinVar
Submissions by phenotype
Xeroderma pigmentosum Uncertain:1
Uncertain significance, criteria provided, single submitter | curation | Sema4, Sema4 | Sep 24, 2021 | - - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 03, 2022 | The c.2545C>G (p.Q849E) alteration is located in exon 11 (coding exon 11) of the ERCC4 gene. This alteration results from a C to G substitution at nucleotide position 2545, causing the glutamine (Q) at amino acid position 849 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Cockayne syndrome;C0268140:Xeroderma pigmentosum, group F;C3808988:Fanconi anemia complementation group Q Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 13, 2024 | - - |
Fanconi anemia complementation group Q Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Victorian Clinical Genetics Services, Murdoch Childrens Research Institute | Oct 19, 2020 | Based on the classification scheme VCGS_Germline_v1.1.1, this variant is classified as likely benign. Following criteria are met: 0102 - Loss-of-function is a known mechanism of disease for this gene. (N) 0106 - This gene is known to be associated with autosomal recessive disease. (N) 0200 - Variant is predicted to result in a missense amino acid change from glutamine to glutamic acid (exon 11). (N) 0252 - Variant is homozygous. (N) 0304 - Variant is present in gnomAD <0.01 for a recessive condition (23 heterozygotes, 1 homozygote). (P) 0309 - An alternative amino acid change at the same position has been observed in gnomAD (p.(Gln849Leu); 9 heterozygotes, 0 homozygotes). (N) 0503 - Missense variant consistently predicted to be tolerated or not conserved in mammals with a minor amino acid change. (B) 0600 - Variant is located in an annotated domain or motif (Rad1 superfamily; NCBI)(N) 0705 - No comparable variants have previous evidence for pathogenicity. (N) 0806 - Moderate previous evidence of neutrality in unrelated individuals (ClinVar). (B) 0905 - No segregation evidence has been identified for this variant. (N) 1007 - No published functional evidence has been identified for this variant. (N) 1205 - Variant is bialleic. (N) Legend: (P) - Pathogenic, (N) - Neutral, (B) - Benign - |
Ovarian cancer Benign:1
Benign, criteria provided, single submitter | clinical testing | Laboratory of Molecular Epidemiology of Birth Defects, West China Second University Hospital, Sichuan University | Jan 01, 2022 | - - |
Xeroderma pigmentosum, group F Benign:1
Likely benign, criteria provided, single submitter | clinical testing | KCCC/NGS Laboratory, Kuwait Cancer Control Center | Jul 07, 2023 | - - |
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