6-43576213-C-A
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBS1_SupportingBS2
The NM_006502.3(POLH):c.-232C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00217 in 209,464 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_006502.3 5_prime_UTR
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
POLH | NM_006502.3 | c.-232C>A | 5_prime_UTR_variant | Exon 1 of 11 | ENST00000372236.9 | NP_006493.1 | ||
XPO5 | NM_020750.3 | c.-349G>T | upstream_gene_variant | ENST00000265351.12 | NP_065801.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00223 AC: 339AN: 152228Hom.: 6 Cov.: 33
GnomAD4 exome AF: 0.00203 AC: 116AN: 57118Hom.: 3 Cov.: 0 AF XY: 0.00187 AC XY: 54AN XY: 28896
GnomAD4 genome AF: 0.00223 AC: 339AN: 152346Hom.: 6 Cov.: 33 AF XY: 0.00319 AC XY: 238AN XY: 74506
ClinVar
Submissions by phenotype
Xeroderma pigmentosum variant type Uncertain:1
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at