Genetic Variant GTF2E1:p.Ser356Ser (chr3-120781218-C-T) – ACMG Classification: Benign (-19 pts)

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_005513.3(GTF2E1):c.1068C>T(p.Ser356Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0126 in 1,614,104 control chromosomes in the GnomAD database, including 141 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0094 ( 3 hom., cov: 32)

Exomes 𝑓: 0.013 ( 138 hom. )

Consequence

GTF2E1
NM_005513.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.271

Variant links:

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]

GTF2E1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.31).

BP6

Variant 3-120781218-C-T is Benign according to our data. Variant chr3-120781218-C-T is described in ClinVar as [Benign]. Clinvar id is 789165.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.271 with no splicing effect.

BS1

Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.0129 (18861/1461824) while in subpopulation MID AF= 0.0371 (214/5768). AF 95% confidence interval is 0.033. There are 138 homozygotes in gnomad4_exome. There are 9279 alleles in male gnomad4_exome subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1439 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GTF2E1	NM_005513.3 link	c.1068C>T	p.Ser356Ser	synonymous_variant	Exon 5 of 5	ENST00000283875.6	NP_005504.2	P29083

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GTF2E1	ENST00000283875.6 link	c.1068C>T	p.Ser356Ser	synonymous_variant	Exon 5 of 5	1	NM_005513.3	ENSP00000283875.5		P29083

Frequencies

GnomAD3 genomes

AF:

0.00947

AC:

1441

AN:

152160

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00420

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00989

Gnomad ASJ

AF:

0.0132

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00517

Gnomad FIN

AF:

0.000754

Gnomad MID

AF:

0.0475

Gnomad NFE

AF:

0.0146

Gnomad OTH

AF:

0.0134

GnomAD3 exomes

AF:

0.00932

AC:

2337

AN:

250884

Hom.:

AF XY:

0.00946

AC XY:

1283

AN XY:

135560

show subpopulations

Gnomad AFR exome

AF:

0.00308

Gnomad AMR exome

AF:

0.0101

Gnomad ASJ exome

AF:

0.0154

Gnomad EAS exome

AF:

0.000544

Gnomad SAS exome

AF:

0.00415

Gnomad FIN exome

AF:

0.00171

Gnomad NFE exome

AF:

0.0135

Gnomad OTH exome

AF:

0.0131

GnomAD4 exome

AF:

0.0129

AC:

18861

AN:

1461824

Hom.:

138

Cov.:

AF XY:

0.0128

AC XY:

9279

AN XY:

727214

show subpopulations

Gnomad4 AFR exome

AF:

0.00335

Gnomad4 AMR exome

AF:

0.0104

Gnomad4 ASJ exome

AF:

0.0159

Gnomad4 EAS exome

AF:

0.000202

Gnomad4 SAS exome

AF:

0.00480

Gnomad4 FIN exome

AF:

0.00161

Gnomad4 NFE exome

AF:

0.0147

Gnomad4 OTH exome

AF:

0.0138

GnomAD4 genome

AF:

0.00945

AC:

1439

AN:

152280

Hom.:

Cov.:

AF XY:

0.00848

AC XY:

631

AN XY:

74444

show subpopulations

Gnomad4 AFR

AF:

0.00419

Gnomad4 AMR

AF:

0.00987

Gnomad4 ASJ

AF:

0.0132

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00538

Gnomad4 FIN

AF:

0.000754

Gnomad4 NFE

AF:

0.0146

Gnomad4 OTH

AF:

0.0128

Alfa

AF:

0.0129

Hom.:

Bravo

AF:

0.0104

Asia WGS

AF:

0.00375

AC:

AN:

3478

EpiCase

AF:

0.0166

EpiControl

AF:

0.0161

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Aug 23, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.31

CADD

Benign

6.2

DANN

Benign

0.88

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