rs875989846

Positions:

• chr8-30612400-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP5

The ENST00000355904.9(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 ENST00000355904.9 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 6.06

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 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 id is 225840.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GTF2E2	NM_002095.6	c.448G>C	p.Ala150Pro	missense_variant	5/8	ENST00000355904.9	NP_002086.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GTF2E2	ENST00000355904.9	c.448G>C	p.Ala150Pro	missense_variant	5/8	1	NM_002095.6	ENSP00000348168	P1
GTF2E2	ENST00000518599.5	c.448G>C	p.Ala150Pro	missense_variant	5/6	5		ENSP00000429921
GTF2E2	ENST00000523499.5	c.*287G>C		3_prime_UTR_variant, NMD_transcript_variant	7/8	4		ENSP00000428981
GTF2E2	ENST00000522833.5			upstream_gene_variant		3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Trichothiodystrophy 6, nonphotosensitive Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

May 09, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.96
BayesDel_addAF	Uncertain	0.071	D
BayesDel_noAF	Benign	-0.14
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.17	T;T
Eigen	Benign	0.14
Eigen_PC	Benign	0.12
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.96	D;D
M_CAP	Benign	0.013	T
MetaRNN	Uncertain	0.44	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.4	M;.
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-1.7	N;N
REVEL	Benign	0.21
Sift	Uncertain	0.020	D;D
Sift4G	Benign	0.13	T;.
Polyphen		0.83	P;.
Vest4		0.82
MutPred		0.46		Loss of MoRF binding (P = 0.0497);Loss of MoRF binding (P = 0.0497);
MVP		0.57
MPC		0.45
ClinPred		0.92	D
GERP RS		4.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.52
gMVP		0.90

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

Other links and lift over

dbSNP: rs875989846; hg19: chr8-30469917;