3-120776634-G-C
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
The NM_005513.3(GTF2E1):c.862G>C(p.Gly288Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000496 in 1,613,522 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000048 ( 0 hom. )
Consequence
GTF2E1
NM_005513.3 missense
NM_005513.3 missense
Scores
6
8
4
Clinical Significance
Conservation
PhyloP100: 9.18
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]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -4 ACMG points.
BS2
?
High AC in GnomAdExome at 6 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GTF2E1 | NM_005513.3 | c.862G>C | p.Gly288Arg | missense_variant | 4/5 | ENST00000283875.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GTF2E1 | ENST00000283875.6 | c.862G>C | p.Gly288Arg | missense_variant | 4/5 | 1 | NM_005513.3 | P1 | |
GTF2E1 | ENST00000469772.5 | c.361G>C | p.Gly121Arg | missense_variant | 3/3 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152198Hom.: 0 Cov.: 32
GnomAD3 genomes
?
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GnomAD3 exomes AF: 0.0000240 AC: 6AN: 250362Hom.: 0 AF XY: 0.0000370 AC XY: 5AN XY: 135284
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GnomAD4 exome AF: 0.00000479 AC: 7AN: 1461324Hom.: 0 Cov.: 31 AF XY: 0.00000550 AC XY: 4AN XY: 726962
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GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152198Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74346
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 01, 2024 | The c.862G>C (p.G288R) alteration is located in exon 4 (coding exon 3) of the GTF2E1 gene. This alteration results from a G to C substitution at nucleotide position 862, causing the glycine (G) at amino acid position 288 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Uncertain
Cadd
Pathogenic
Dann
Pathogenic
DEOGEN2
Benign
T;T
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D
M_CAP
Benign
D
MetaRNN
Uncertain
D;D
MetaSVM
Benign
T
MutationTaster
Benign
D
PrimateAI
Pathogenic
D
PROVEAN
Uncertain
D;N
REVEL
Uncertain
Sift
Uncertain
D;D
Sift4G
Uncertain
D;T
Polyphen
0.99
.;D
Vest4
0.88
MutPred
0.43
.;Gain of glycosylation at Y290 (P = 4e-04);
MVP
MPC
0.55
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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Calibrated prediction
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at