6-158191983-TG-T
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Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PVS1_StrongPM2PP5_Moderate
The NM_207118.3(GTF2H5):c.43del(p.Ala15ProfsTer2) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★).
Frequency
Genomes: not found (cov: 32)
Consequence
GTF2H5
NM_207118.3 frameshift
NM_207118.3 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 7.81
Genes affected
GTF2H5 (HGNC:21157): (general transcription factor IIH subunit 5) This gene encodes a subunit of transcription/repair factor TFIIH, which functions in gene transcription and DNA repair. This protein stimulates ERCC3/XPB ATPase activity to trigger DNA opening during DNA repair, and is implicated in regulating cellular levels of TFIIH. Mutations in this gene result in trichothiodystrophy, complementation group A. [provided by RefSeq, Mar 2009]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 8 ACMG points.
PVS1
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. There are 5 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 6-158191983-TG-T is Pathogenic according to our data. Variant chr6-158191983-TG-T is described in ClinVar as [Pathogenic]. Clinvar id is 1382813.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GTF2H5 | NM_207118.3 | c.43del | p.Ala15ProfsTer2 | frameshift_variant | 3/3 | ENST00000607778.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GTF2H5 | ENST00000607778.2 | c.43del | p.Ala15ProfsTer2 | frameshift_variant | 3/3 | 1 | NM_207118.3 | P1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome Cov.: 30
GnomAD4 exome
Cov.:
30
GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Aug 19, 2022 | For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the GTF2H5 protein in which other variant(s) (p.Arg56*) have been determined to be pathogenic (PMID: 15220921, 25620205). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. ClinVar contains an entry for this variant (Variation ID: 1382813). This variant has not been reported in the literature in individuals affected with GTF2H5-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Ala15Profs*2) in the GTF2H5 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 57 amino acid(s) of the GTF2H5 protein. - |
Computational scores
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Calibrated prediction
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Prediction
Splicing
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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.