rs767569346
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7
The NM_004628.5(XPC):c.1677C>T(p.Tyr559=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000143 in 1,613,812 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 Likely benign (★).
Frequency
Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000014 ( 0 hom. )
Consequence
XPC
NM_004628.5 synonymous
NM_004628.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.74
Genes affected
XPC (HGNC:12816): (XPC complex subunit, DNA damage recognition and repair factor) The protein encoded by this gene is a key component of the XPC complex, which plays an important role in the early steps of global genome nucleotide excision repair (NER). The encoded protein is important for damage sensing and DNA binding, and shows a preference for single-stranded DNA. Mutations in this gene or some other NER components can result in Xeroderma pigmentosum, a rare autosomal recessive disorder characterized by increased sensitivity to sunlight with the development of carcinomas at an early age. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Aug 2017]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -5 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.67).
BP6
?
Variant 3-14158206-G-A is Benign according to our data. Variant chr3-14158206-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1091375.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=1.74 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
XPC | NM_004628.5 | c.1677C>T | p.Tyr559= | synonymous_variant | 9/16 | ENST00000285021.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
XPC | ENST00000285021.12 | c.1677C>T | p.Tyr559= | synonymous_variant | 9/16 | 1 | NM_004628.5 | P1 | |
XPC-AS1 | ENST00000627116.2 | n.457-7670G>A | intron_variant, non_coding_transcript_variant | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152100Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000120 AC: 3AN: 249362Hom.: 0 AF XY: 0.00000739 AC XY: 1AN XY: 135250
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GnomAD4 exome AF: 0.0000137 AC: 20AN: 1461712Hom.: 0 Cov.: 30 AF XY: 0.00000963 AC XY: 7AN XY: 727138
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GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152100Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74278
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Nov 17, 2023 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at