19-6380376-C-T
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Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2
The NM_002096.3(GTF2F1):c.1459G>A(p.Glu487Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000616 in 1,461,878 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000062 ( 0 hom. )
Consequence
GTF2F1
NM_002096.3 missense
NM_002096.3 missense
Scores
1
10
8
Clinical Significance
Conservation
PhyloP100: 5.40
Genes affected
GTF2F1 (HGNC:4652): (general transcription factor IIF subunit 1) Enables several functions, including RNA polymerase II general transcription initiation factor activity; phosphatase activator activity; and promoter-specific chromatin binding activity. Involved in several processes, including positive regulation of transcription by RNA polymerase II; response to virus; and transcription initiation from RNA polymerase II promoter. Located in cell junction and nucleoplasm. Part of transcription factor TFIID 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 -5 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.38642398).
BS2
High AC in GnomAdExome4 at 9 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GTF2F1 | NM_002096.3 | c.1459G>A | p.Glu487Lys | missense_variant | 13/13 | ENST00000394456.10 | |
GTF2F1 | XM_047438710.1 | c.1486G>A | p.Glu496Lys | missense_variant | 12/12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GTF2F1 | ENST00000394456.10 | c.1459G>A | p.Glu487Lys | missense_variant | 13/13 | 1 | NM_002096.3 | P1 | |
GTF2F1 | ENST00000593678.5 | c.1207G>A | p.Glu403Lys | missense_variant | 10/10 | 2 | |||
GTF2F1 | ENST00000594213.5 | n.816G>A | non_coding_transcript_exon_variant | 6/6 | 3 | ||||
GTF2F1 | ENST00000594965.1 | downstream_gene_variant | 3 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD3 exomes AF: 0.00000795 AC: 2AN: 251496Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135922
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GnomAD4 exome AF: 0.00000616 AC: 9AN: 1461878Hom.: 0 Cov.: 32 AF XY: 0.00000413 AC XY: 3AN XY: 727242
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GnomAD4 genome Cov.: 32
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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 11, 2024 | The c.1459G>A (p.E487K) alteration is located in exon 13 (coding exon 13) of the GTF2F1 gene. This alteration results from a G to A substitution at nucleotide position 1459, causing the glutamic acid (E) at amino acid position 487 to be replaced by a lysine (K). 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
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;.
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;.
REVEL
Benign
Sift
Uncertain
D;.
Sift4G
Uncertain
D;D
Polyphen
P;.
Vest4
MutPred
Gain of MoRF binding (P = 0.0016);.;
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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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