3-120770878-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_005513.3(GTF2E1):​c.599C>G​(p.Ala200Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,346 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A200S) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

GTF2E1
NM_005513.3 missense

Scores

3
7
9

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.91
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 Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GTF2E1NM_005513.3 linkc.599C>G p.Ala200Gly missense_variant Exon 3 of 5 ENST00000283875.6 NP_005504.2 P29083

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
GTF2E1ENST00000283875.6 linkc.599C>G p.Ala200Gly missense_variant Exon 3 of 5 1 NM_005513.3 ENSP00000283875.5 P29083
GTF2E1ENST00000469772.5 linkc.98C>G p.Ala33Gly missense_variant Exon 2 of 3 5 ENSP00000418808.1 C9IYL4

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251332
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135832
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000880
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461346
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
726998
show subpopulations
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:
9.00e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Feb 10, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.599C>G (p.A200G) alteration is located in exon 3 (coding exon 2) of the GTF2E1 gene. This alteration results from a C to G substitution at nucleotide position 599, causing the alanine (A) at amino acid position 200 to be replaced by a glycine (G). 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
0.43
BayesDel_addAF
Benign
-0.022
T
BayesDel_noAF
Benign
-0.27
CADD
Pathogenic
28
DANN
Uncertain
1.0
DEOGEN2
Benign
0.24
T;T
Eigen
Pathogenic
0.83
Eigen_PC
Pathogenic
0.84
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.94
D;D
M_CAP
Benign
0.018
T
MetaRNN
Uncertain
0.57
D;D
MetaSVM
Benign
-0.55
T
MutationAssessor
Benign
2.0
.;M
PrimateAI
Uncertain
0.62
T
PROVEAN
Uncertain
-3.0
D;D
REVEL
Benign
0.25
Sift
Uncertain
0.025
D;D
Sift4G
Benign
0.18
T;T
Polyphen
0.97
.;D
Vest4
0.45
MutPred
0.56
.;Gain of glycosylation at Y201 (P = 0.0166);
MVP
0.27
MPC
0.34
ClinPred
0.73
D
GERP RS
5.8
Varity_R
0.38
gMVP
0.38

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: rs760649397; hg19: chr3-120489725; API