8-30612398-GGC-TGG

Variant names:

• chr8-30612398-GGC-TGG
• NM_002095.6:c.448_450delGCCinsCCA
• GTF2E2 p.Ala150Pro

Variant summary

Our verdict is Uncertain significance. The variant received 5 ACMG points: 5P and 0B. PS1 PP3

The NM_002095.6(GTF2E2):​c.448_450delGCCinsCCA​(p.Ala150Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Pathogenic in ClinVar. 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.89
• Publications: 0 publications found

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, Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
• trichothiodystrophy

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 5 ACMG points.

• PS1: Transcript NM_002095.6 (GTF2E2) is affected with MISSENSE_VARIANT having same AA change as one Pathogenic present in ClinVar.
• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GTF2E2	NM_002095.6	MANE Select	c.448_450delGCCinsCCA	p.Ala150Pro	missense	N/A	NP_002086.1	P29084
	GTF2E2	NM_001348353.1		c.448_450delGCCinsCCA	p.Ala150Pro	missense	N/A	NP_001335282.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GTF2E2	ENST00000355904.9	TSL:1 MANE Select	c.448_450delGCCinsCCA	p.Ala150Pro	missense	N/A	ENSP00000348168.4	P29084
	GTF2E2	ENST00000868892.1		c.448_450delGCCinsCCA	p.Ala150Pro	missense	N/A	ENSP00000538951.1
	GTF2E2	ENST00000868887.1		c.532_534delGCCinsCCA	p.Ala178Pro	missense	N/A	ENSP00000538946.1

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		9.9

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr8-30469915;