rs761564262
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP5_Moderate
The NM_006297.3(XRCC1):āc.1293G>Cā(p.Lys431Asn) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000151 in 1,461,682 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Likely pathogenic (ā ).
Frequency
Consequence
NM_006297.3 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
XRCC1 | NM_006297.3 | c.1293G>C | p.Lys431Asn | missense_variant, splice_region_variant | 11/17 | ENST00000262887.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
XRCC1 | ENST00000262887.10 | c.1293G>C | p.Lys431Asn | missense_variant, splice_region_variant | 11/17 | 1 | NM_006297.3 | P1 | |
XRCC1 | ENST00000543982.5 | c.1200G>C | p.Lys400Asn | missense_variant, splice_region_variant | 10/16 | 2 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.0000319 AC: 8AN: 251088Hom.: 0 AF XY: 0.0000368 AC XY: 5AN XY: 135702
GnomAD4 exome AF: 0.0000151 AC: 22AN: 1461682Hom.: 1 Cov.: 33 AF XY: 0.0000220 AC XY: 16AN XY: 727140
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Spinocerebellar ataxia, autosomal recessive 26 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Aug 22, 2017 | - - |
not provided Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Dec 02, 2023 | The last nucleotide of exon variant in a gene for which loss of function is a known mechanism of disease, and both splice predictors and evolutionary conservation support a deleterious effect, although in the absence of functional evidence the actual effect of this sequence change is unknown.; In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 34339737, 33163565, 29472272, 31374202, 28002403) - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at