Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP5

The NM_002095.6(GTF2E2):c.448G>C(p.Ala150Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars). Synonymous variant affecting the same amino acid position (i.e. A150A) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Consequence

GTF2E2
NM_002095.6 missense

Scores

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 6.06

Publications

5 publications found

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 Gene-Disease associations (from GenCC):

trichothiodystrophy 6, nonphotosensitive
Inheritance: AR Classification: STRONG, MODERATE Submitted by: Genomics England PanelApp, G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
trichothiodystrophy
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

GTF2E2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP5

Variant 8-30612400-C-G is Pathogenic according to our data. Variant chr8-30612400-C-G is described in ClinVar as Pathogenic. ClinVar VariationId is 225840.Status of the report is no_assertion_criteria_provided, 0 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002095.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GTF2E2	NM_002095.6	MANE Select	c.448G>C	p.Ala150Pro	missense	Exon 5 of 8	NP_002086.1
	GTF2E2	NM_001348353.1		c.448G>C	p.Ala150Pro	missense	Exon 5 of 7	NP_001335282.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
GTF2E2	ENST00000355904.9	TSL:1 MANE Select	c.448G>C	p.Ala150Pro	missense	Exon 5 of 8	ENSP00000348168.4
GTF2E2	ENST00000518599.5	TSL:5	c.448G>C	p.Ala150Pro	missense	Exon 5 of 6	ENSP00000429921.1
GTF2E2	ENST00000523499.5	TSL:4	n.*287G>C		non_coding_transcript_exon	Exon 7 of 8	ENSP00000428981.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions as Germline

Significance:Pathogenic

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

Trichothiodystrophy 6, nonphotosensitive (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.96

BayesDel_addAF

Uncertain

0.071

BayesDel_noAF

Benign

-0.14

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.17

Eigen

Benign

0.14

Eigen_PC

Benign

0.12

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.96

M_CAP

Benign

0.013

MetaRNN

Uncertain

0.44

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.4

PhyloP100

6.1

PrimateAI

Uncertain

0.61

PROVEAN

Benign

-1.7

REVEL

Benign

0.21

Sift

Uncertain

0.020

Sift4G

Benign

0.13

Polyphen

0.83

Vest4

0.82

MutPred

0.46

Loss of MoRF binding (P = 0.0497)

MVP

0.57

MPC

0.45

ClinPred

0.92

GERP RS

4.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.52

gMVP

0.90

Mutation Taster

=11/89

disease causing (ClinVar)

(source)

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

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NM_002095.6:c.448G>C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over