3-120781065-T-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_005513.3(GTF2E1):c.915T>G(p.Phe305Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,461,016 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: GTF2E1 NM_005513.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.378

Genes affected

GTF2E1 (HGNC:4650): (general transcription factor IIE subunit 1) Enables RNA polymerase II general transcription initiation factor activity. Involved in transcription by RNA polymerase II. Located in cytosol and nucleoplasm. Part of transcription factor TFIID complex and transcription preinitiation complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.094946295).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GTF2E1	NM_005513.3	c.915T>G	p.Phe305Leu	missense_variant	5/5	ENST00000283875.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GTF2E1	ENST00000283875.6	c.915T>G	p.Phe305Leu	missense_variant	5/5	1	NM_005513.3	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000479 AC: 7 AN: 1461016 Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3 AN XY: 726722

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: 0.00000630

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 11, 2023

The c.915T>G (p.F305L) alteration is located in exon 5 (coding exon 4) of the GTF2E1 gene. This alteration results from a T to G substitution at nucleotide position 915, causing the phenylalanine (F) at amino acid position 305 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.47
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
Cadd	Benign	17
Dann	Benign	0.95
DEOGEN2	Benign	0.0097	T
Eigen	Benign	-0.18
Eigen_PC	Benign	-0.050
FATHMM_MKL	Uncertain	0.76	D
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.0077	T
MetaRNN	Benign	0.095	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.0	L
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-0.65	N
REVEL	Benign	0.13
Sift	Benign	0.57	T
Sift4G	Benign	0.65	T
Polyphen		0.0010	B
Vest4		0.096
MutPred		0.31		Gain of helix (P = 0.0854);
MVP		0.36
MPC		0.33
ClinPred		0.32	T
GERP RS		4.0
Varity_R		0.15
gMVP		0.094

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-120499912;