chr6-43582370-TTTTG-T
Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1PM2PP5
The NM_006502.3(POLH):c.54_57del(p.Val19LysfsTer10) variant causes a frameshift change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars).
Frequency
Genomes: not found (cov: 32)
Consequence
POLH
NM_006502.3 frameshift
NM_006502.3 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 6.78
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]
POLR1C (HGNC:20194): (RNA polymerase I and III subunit C) The protein encoded by this gene is a subunit of both RNA polymerase I and RNA polymerase III complexes. The encoded protein is part of the Pol core element. Mutations in this gene have been associated with Treacher Collins syndrome (TCS) and hypomyelinating leukodystrophy 11. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 11 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 41 pathogenic variants in the truncated region.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 6-43582370-TTTTG-T is Pathogenic according to our data. Variant chr6-43582370-TTTTG-T is described in ClinVar as [Pathogenic]. Clinvar id is 5885.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
POLH | NM_006502.3 | c.54_57del | p.Val19LysfsTer10 | frameshift_variant | 2/11 | ENST00000372236.9 | |
POLH | NM_001291970.2 | c.54_57del | p.Val19LysfsTer10 | frameshift_variant | 2/11 | ||
POLH | NM_001291969.2 | c.-17-634_-17-631del | intron_variant | ||||
POLR1C | NM_001318876.2 | c.945+53102_945+53105del | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
POLH | ENST00000372236.9 | c.54_57del | p.Val19LysfsTer10 | frameshift_variant | 2/11 | 1 | NM_006502.3 | P1 | |
POLH | ENST00000372226.1 | c.54_57del | p.Val19LysfsTer10 | frameshift_variant | 2/11 | 1 | |||
POLH | ENST00000443535.1 | c.-49-634_-49-631del | intron_variant | 2 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Xeroderma pigmentosum variant type Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Jun 17, 1999 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.