chr3-14152358-T-TCAC
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PM4_Supporting
The NM_004628.5(XPC):c.2089_2091dupGTG(p.Val697dup) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000186 in 1,613,226 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_004628.5 conservative_inframe_insertion
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152144Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000403 AC: 1AN: 247934Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 134514
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461082Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0AN XY: 726742
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152144Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74318
ClinVar
Submissions by phenotype
not specified Uncertain:1
Variant summary: XPC c.2089_2091dupGTG (p.Val697dup) results in an in-frame duplication that is predicted to duplicate one amino acids into the encoded protein. The variant allele was found at a frequency of 4e-06 in 247934 control chromosomes. c.2089_2091dupGTG has been reported in the literature in individuals affected with Xeroderma Pigmentosum (Li_1993, Soufir_2009). These data do not allow any conclusion about variant significance. At least one publication reports experimental evidence evaluating an impact on protein function suggestive of an effect on function (Bernardes_2008). However, additional data is needed to make a conclusion about variant significance. The following publications have been ascertained in the context of this evaluation (PMID: 18809580, 8298653, 20054342). ClinVar contains an entry for this variant (Variation ID: 553916). Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic. -
Xeroderma pigmentosum, group C Uncertain:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at