8-30607141-C-A
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2PP3PP5_Moderate
The NM_002095.6(GTF2E2):c.559G>T(p.Asp187Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★). Synonymous variant affecting the same amino acid position (i.e. D187D) has been classified as Likely benign.
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
GTF2E2
NM_002095.6 missense
NM_002095.6 missense
Scores
7
8
4
Clinical Significance
Conservation
PhyloP100: 7.85
Genes affected
GTF2E2 (HGNC:4651): (general transcription factor IIE subunit 2) The general transcription factor IIE (TFIIE) is part of the RNA polymerase II transcription initiation complex, recruiting TFIIH and being essential for promoter clearance by RNA polymerase II. TFIIE is a heterodimer (and sometimes heterotetramer) of alpha and beta subunits. The protein encoded by this gene represents the beta subunit of TFIIE. [provided by RefSeq, Jan 2017]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 5 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.797
PP5
Variant 8-30607141-C-A is Pathogenic according to our data. Variant chr8-30607141-C-A is described in ClinVar as [Pathogenic]. Clinvar id is 225841.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr8-30607141-C-A is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GTF2E2 | NM_002095.6 | c.559G>T | p.Asp187Tyr | missense_variant | 6/8 | ENST00000355904.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GTF2E2 | ENST00000355904.9 | c.559G>T | p.Asp187Tyr | missense_variant | 6/8 | 1 | NM_002095.6 | P1 | |
GTF2E2 | ENST00000518599.5 | c.559G>T | p.Asp187Tyr | missense_variant | 6/6 | 5 | |||
GTF2E2 | ENST00000522833.5 | n.77G>T | non_coding_transcript_exon_variant | 2/4 | 3 | ||||
GTF2E2 | ENST00000523499.5 | c.*398G>T | 3_prime_UTR_variant, NMD_transcript_variant | 8/8 | 4 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1189280Hom.: 0 Cov.: 16 AF XY: 0.00 AC XY: 0AN XY: 602408
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
AC:
0
AN:
1189280
Hom.:
Cov.:
16
AF XY:
AC XY:
0
AN XY:
602408
Gnomad4 AFR exome
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GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:2
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Trichothiodystrophy 6, nonphotosensitive Pathogenic:2
Pathogenic, no assertion criteria provided | literature only | OMIM | May 09, 2016 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Institute of Human Genetics, Clinical Exome/Genome Diagnostics Group, University Hospital Bonn | Apr 14, 2023 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
T;T
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D
M_CAP
Benign
D
MetaRNN
Pathogenic
D;D
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;.
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D
REVEL
Uncertain
Sift
Uncertain
D;D
Sift4G
Uncertain
D;.
Polyphen
D;.
Vest4
MutPred
Gain of helix (P = 0.0143);Gain of helix (P = 0.0143);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
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