Menu
GeneBe

3-120781218-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BS1BS2

The NM_005513.3(GTF2E1):c.1068C>T(p.Ser356=) 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

2

Clinical Significance

Benign criteria provided, single submitter B:1

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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.31).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
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_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=0.271 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
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
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 1441 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
GTF2E1NM_005513.3 linkuse as main transcriptc.1068C>T p.Ser356= synonymous_variant 5/5 ENST00000283875.6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
GTF2E1ENST00000283875.6 linkuse as main transcriptc.1068C>T p.Ser356= synonymous_variant 5/51 NM_005513.3 P1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00947
AC:
1441
AN:
152160
Hom.:
3
Cov.:
32
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.:
21
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.:
32
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
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00945
AC:
1439
AN:
152280
Hom.:
3
Cov.:
32
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.:
4
Bravo
AF:
0.0104
Asia WGS
AF:
0.00375
AC:
14
AN:
3478
EpiCase
AF:
0.0166
EpiControl
AF:
0.0161

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeAug 23, 2018- -

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.

Other links and lift over

dbSNP: rs17243695; hg19: chr3-120500065; COSMIC: COSV99381826; COSMIC: COSV99381826; API