19-6380324-C-T
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Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_002096.3(GTF2F1):c.1511G>A(p.Arg504His) variant causes a missense change. The variant allele was found at a frequency of 0.0000954 in 1,614,094 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: 𝑓 0.000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000099 ( 0 hom. )
Consequence
GTF2F1
NM_002096.3 missense
NM_002096.3 missense
Scores
2
6
11
Clinical Significance
Conservation
PhyloP100: 5.45
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 -6 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.11881855).
BS2
High AC in GnomAd4 at 10 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GTF2F1 | NM_002096.3 | c.1511G>A | p.Arg504His | missense_variant | 13/13 | ENST00000394456.10 | |
GTF2F1 | XM_047438710.1 | c.1538G>A | p.Arg513His | missense_variant | 12/12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GTF2F1 | ENST00000394456.10 | c.1511G>A | p.Arg504His | missense_variant | 13/13 | 1 | NM_002096.3 | P1 | |
GTF2F1 | ENST00000593678.5 | c.1259G>A | p.Arg420His | missense_variant | 10/10 | 2 | |||
GTF2F1 | ENST00000594213.5 | n.868G>A | non_coding_transcript_exon_variant | 6/6 | 3 |
Frequencies
GnomAD3 genomes AF: 0.0000657 AC: 10AN: 152094Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000835 AC: 21AN: 251496Hom.: 0 AF XY: 0.0000809 AC XY: 11AN XY: 135922
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GnomAD4 exome AF: 0.0000985 AC: 144AN: 1461882Hom.: 0 Cov.: 31 AF XY: 0.0000866 AC XY: 63AN XY: 727240
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GnomAD4 genome AF: 0.0000657 AC: 10AN: 152212Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3AN XY: 74428
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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 | Feb 14, 2023 | The c.1511G>A (p.R504H) 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 1511, causing the arginine (R) at amino acid position 504 to be replaced by a histidine (H). 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
Pathogenic
DANN
Pathogenic
DEOGEN2
Benign
T;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T
M_CAP
Benign
D
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
MVP
MPC
ClinPred
T
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