rs1260189637
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_004628.5(XPC):βc.128delβ(p.Pro43GlnfsTer36) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000501 in 1,595,786 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (β β ). Synonymous variant affecting the same amino acid position (i.e. P43P) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_004628.5 frameshift
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
XPC | NM_004628.5 | c.128del | p.Pro43GlnfsTer36 | frameshift_variant | 2/16 | ENST00000285021.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
XPC | ENST00000285021.12 | c.128del | p.Pro43GlnfsTer36 | frameshift_variant | 2/16 | 1 | NM_004628.5 | P1 | |
XPC | ENST00000476581.6 | c.128del | p.Pro43GlnfsTer36 | frameshift_variant, NMD_transcript_variant | 2/15 | 1 | |||
XPC | ENST00000511155.1 | c.110del | p.Pro37GlnfsTer36 | frameshift_variant | 2/4 | 4 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152176Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000451 AC: 1AN: 221932Hom.: 0 AF XY: 0.00000833 AC XY: 1AN XY: 120120
GnomAD4 exome AF: 0.00000416 AC: 6AN: 1443610Hom.: 0 Cov.: 30 AF XY: 0.00000279 AC XY: 2AN XY: 717158
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152176Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74350
ClinVar
Submissions by phenotype
not provided Pathogenic:2
Pathogenic, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jul 01, 2018 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Oct 04, 2023 | This sequence change creates a premature translational stop signal (p.Pro43Glnfs*36) in the XPC gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in XPC are known to be pathogenic (PMID: 23173980, 25256075). This variant is present in population databases (no rsID available, gnomAD 0.003%). This premature translational stop signal has been observed in individuals with xeroderma pigmentosum (PMID: 10766188). This variant is also known as fs43>378stop. ClinVar contains an entry for this variant (Variation ID: 551235). For these reasons, this variant has been classified as Pathogenic. - |
Xeroderma pigmentosum, group C Pathogenic:2
Pathogenic, criteria provided, single submitter | clinical testing | Baylor Genetics | Jan 02, 2024 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Counsyl | Apr 03, 2017 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at