19-6380286-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_002096.3(GTF2F1):​c.1549G>A​(p.Glu517Lys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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)

Consequence

GTF2F1
NM_002096.3 missense

Scores

3
5
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.28
Variant links:
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 Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.37350872).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GTF2F1NM_002096.3 linkc.1549G>A p.Glu517Lys missense_variant Exon 13 of 13 ENST00000394456.10 NP_002087.2 P35269
GTF2F1XM_047438710.1 linkc.1576G>A p.Glu526Lys missense_variant Exon 12 of 12 XP_047294666.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
GTF2F1ENST00000394456.10 linkc.1549G>A p.Glu517Lys missense_variant Exon 13 of 13 1 NM_002096.3 ENSP00000377969.3 P35269
GTF2F1ENST00000593678.5 linkc.1297G>A p.Glu433Lys missense_variant Exon 10 of 10 2 ENSP00000469091.1 M0QXD6
GTF2F1ENST00000594213.5 linkn.906G>A non_coding_transcript_exon_variant Exon 6 of 6 3
GTF2F1ENST00000594965.1 linkn.*105G>A downstream_gene_variant 3

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
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 06, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1549G>A (p.E517K) 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 1549, causing the glutamic acid (E) at amino acid position 517 to be replaced by a lysine (K). 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
Pathogenic
0.76
BayesDel_addAF
Benign
-0.058
T
BayesDel_noAF
Benign
-0.32
CADD
Pathogenic
28
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.082
T;T
Eigen
Uncertain
0.46
Eigen_PC
Uncertain
0.48
FATHMM_MKL
Uncertain
0.92
D
LIST_S2
Uncertain
0.90
D;D
M_CAP
Benign
0.023
T
MetaRNN
Benign
0.37
T;T
MetaSVM
Benign
-0.51
T
MutationAssessor
Benign
1.9
L;.
PrimateAI
Uncertain
0.64
T
PROVEAN
Benign
-1.1
N;.
REVEL
Benign
0.16
Sift
Pathogenic
0.0
D;.
Sift4G
Benign
0.15
T;T
Polyphen
0.62
P;.
Vest4
0.17
MutPred
0.54
Gain of MoRF binding (P = 2e-04);.;
MVP
0.68
MPC
0.41
ClinPred
0.91
D
GERP RS
4.6
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.90
gMVP
0.54

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-6380297; API