9-97675443-A-AT
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PVS1_ModeratePM2
The NM_000380.4(XPA):c.817dupA(p.Met273AsnfsTer5) variant causes a frameshift change. The variant allele was found at a frequency of 0.00000124 in 1,612,848 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_000380.4 frameshift
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
XPA | ENST00000375128.5 | c.817dupA | p.Met273AsnfsTer5 | frameshift_variant | Exon 6 of 6 | 1 | NM_000380.4 | ENSP00000364270.5 | ||
XPA | ENST00000462523.5 | n.*253dupA | non_coding_transcript_exon_variant | Exon 7 of 7 | 5 | ENSP00000433006.1 | ||||
XPA | ENST00000485042.1 | n.329dupA | non_coding_transcript_exon_variant | Exon 2 of 2 | 3 | |||||
XPA | ENST00000462523.5 | n.*253dupA | 3_prime_UTR_variant | Exon 7 of 7 | 5 | ENSP00000433006.1 |
Frequencies
GnomAD3 genomes AF: 0.00000658 AC: 1AN: 151956Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000799 AC: 2AN: 250256Hom.: 0 AF XY: 0.00000740 AC XY: 1AN XY: 135180
GnomAD4 exome AF: 6.85e-7 AC: 1AN: 1460892Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 726586
GnomAD4 genome AF: 0.00000658 AC: 1AN: 151956Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74216
ClinVar
Submissions by phenotype
not specified Uncertain:1
Variant summary: XPA c.817dupA (p.Met273AsnfsX5) causes a frameshift which results in an extension of the protein, which replaced the last amino acid with 4 different amino acids. The variant allele was found at a frequency of 8e-06 in 250256 control chromosomes. To our knowledge, no occurrence of c.817dupA in individuals affected with Xeroderma Pigmentosum and no experimental evidence demonstrating its impact on protein function have been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance. -
Xeroderma pigmentosum group A Uncertain:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at