Variant rs875989847 details in Genebe, Genetics Data Aggregator

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

Scores

Clinical Significance

Pathogenic criteria provided, single submitter P:2

Conservation

PhyloP100: 7.85

Variant links:

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]

GTF2E2 links:

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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 linkuse as main transcript	c.559G>T	p.Asp187Tyr	missense_variant	6/8	ENST00000355904.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
GTF2E2	ENST00000355904.9 linkuse as main transcript	c.559G>T	p.Asp187Tyr	missense_variant	6/8	1	NM_002095.6	P1
GTF2E2	ENST00000518599.5 linkuse as main transcript	c.559G>T	p.Asp187Tyr	missense_variant	6/6	5
GTF2E2	ENST00000522833.5 linkuse as main transcript	n.77G>T		non_coding_transcript_exon_variant	2/4	3
GTF2E2	ENST00000523499.5 linkuse as main transcript	c.*398G>T		3_prime_UTR_variant, NMD_transcript_variant	8/8	4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1189280

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

602408

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.71

BayesDel_addAF

Pathogenic

0.22

BayesDel_noAF

Uncertain

0.070

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.26

T;T

Eigen

Pathogenic

0.89

Eigen_PC

Pathogenic

0.87

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.95

D;D

M_CAP

Benign

0.059

MetaRNN

Pathogenic

0.80

D;D

MetaSVM

Benign

-0.61

MutationAssessor

Uncertain

2.5

M;.

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.72

PROVEAN

Pathogenic

-5.0

D;D

REVEL

Uncertain

0.50

Sift

Uncertain

0.0090

D;D

Sift4G

Uncertain

0.016

D;.

Polyphen

1.0

D;.

Vest4

0.94

MutPred

0.43

Gain of helix (P = 0.0143);Gain of helix (P = 0.0143);

MVP

0.73

MPC

0.97

ClinPred

0.99

GERP RS

5.7

Varity_R

0.72

gMVP

0.72

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over