6-43582338-C-T
Variant names:
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_006502.3(POLH):c.19C>T(p.Arg7*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000496 in 1,613,960 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★).
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000041 ( 0 hom. )
Consequence
POLH
NM_006502.3 stop_gained
NM_006502.3 stop_gained
Scores
4
2
1
Clinical Significance
Conservation
PhyloP100: 3.04
Genes affected
POLH (HGNC:9181): (DNA polymerase eta) This gene encodes a member of the Y family of specialized DNA polymerases. It copies undamaged DNA with a lower fidelity than other DNA-directed polymerases. However, it accurately replicates UV-damaged DNA; when thymine dimers are present, this polymerase inserts the complementary nucleotides in the newly synthesized DNA, thereby bypassing the lesion and suppressing the mutagenic effect of UV-induced DNA damage. This polymerase is thought to be involved in hypermutation during immunoglobulin class switch recombination. Mutations in this gene result in XPV, a variant type of xeroderma pigmentosum. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2014]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 12 ACMG points.
PVS1
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 45 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 6-43582338-C-T is Pathogenic according to our data. Variant chr6-43582338-C-T is described in ClinVar as [Likely_pathogenic]. Clinvar id is 3593646.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
POLH | NM_006502.3 | c.19C>T | p.Arg7* | stop_gained | Exon 2 of 11 | ENST00000372236.9 | NP_006493.1 | |
POLH | NM_001291970.2 | c.19C>T | p.Arg7* | stop_gained | Exon 2 of 11 | NP_001278899.1 | ||
POLH | NM_001291969.2 | c.-17-669C>T | intron_variant | Intron 1 of 8 | NP_001278898.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
POLH | ENST00000372236.9 | c.19C>T | p.Arg7* | stop_gained | Exon 2 of 11 | 1 | NM_006502.3 | ENSP00000361310.4 | ||
POLH | ENST00000372226.1 | c.19C>T | p.Arg7* | stop_gained | Exon 2 of 11 | 1 | ENSP00000361300.1 | |||
POLH | ENST00000443535.1 | c.-49-669C>T | intron_variant | Intron 1 of 2 | 2 | ENSP00000405320.1 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152164Hom.: 0 Cov.: 32
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GnomAD4 exome AF: 0.00000410 AC: 6AN: 1461796Hom.: 0 Cov.: 32 AF XY: 0.00000550 AC XY: 4AN XY: 727212
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GnomAD4 genome AF: 0.0000131 AC: 2AN: 152164Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74322
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ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Xeroderma pigmentosum variant type Pathogenic:1
Jan 14, 2024
Fulgent Genetics, Fulgent Genetics
Significance: Likely pathogenic
Review Status: criteria provided, single submitter
Collection Method: clinical testing
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Computational scores
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Name
Calibrated prediction
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BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
Vest4
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at