19-6380339-C-T

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_002096.3(GTF2F1):​c.1496G>A​(p.Arg499Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000124 in 1,614,100 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 0.0000066 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000013 ( 0 hom. )

Consequence

GTF2F1
NM_002096.3 missense

Scores

1
8
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.33
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.29087743).
BS2
High AC in GnomAdExome4 at 19 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GTF2F1NM_002096.3 linkc.1496G>A p.Arg499Gln missense_variant Exon 13 of 13 ENST00000394456.10 NP_002087.2 P35269
GTF2F1XM_047438710.1 linkc.1523G>A p.Arg508Gln 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.1496G>A p.Arg499Gln missense_variant Exon 13 of 13 1 NM_002096.3 ENSP00000377969.3 P35269
GTF2F1ENST00000593678.5 linkc.1244G>A p.Arg415Gln missense_variant Exon 10 of 10 2 ENSP00000469091.1 M0QXD6
GTF2F1ENST00000594213.5 linkn.853G>A non_coding_transcript_exon_variant Exon 6 of 6 3
GTF2F1ENST00000594965.1 linkn.*52G>A downstream_gene_variant 3

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152096
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000278
AC:
7
AN:
251496
Hom.:
0
AF XY:
0.0000294
AC XY:
4
AN XY:
135922
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:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000527
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000130
AC:
19
AN:
1461886
Hom.:
0
Cov.:
32
AF XY:
0.0000138
AC XY:
10
AN XY:
727244
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000144
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152214
Hom.:
0
Cov.:
31
AF XY:
0.0000134
AC XY:
1
AN XY:
74428
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
ExAC
AF:
0.0000412
AC:
5
EpiCase
AF:
0.0000545
EpiControl
AF:
0.0000593

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Aug 22, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1496G>A (p.R499Q) 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 1496, causing the arginine (R) at amino acid position 499 to be replaced by a glutamine (Q). 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
0.35
BayesDel_addAF
Benign
-0.18
T
BayesDel_noAF
Benign
-0.32
CADD
Pathogenic
31
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.12
T;T
Eigen
Uncertain
0.49
Eigen_PC
Uncertain
0.45
FATHMM_MKL
Uncertain
0.94
D
LIST_S2
Uncertain
0.94
D;D
M_CAP
Benign
0.026
D
MetaRNN
Benign
0.29
T;T
MetaSVM
Benign
-0.69
T
MutationAssessor
Uncertain
2.3
M;.
PrimateAI
Uncertain
0.65
T
PROVEAN
Benign
-1.5
N;.
REVEL
Benign
0.23
Sift
Benign
0.034
D;.
Sift4G
Uncertain
0.037
D;T
Polyphen
1.0
D;.
Vest4
0.48
MVP
0.77
MPC
0.96
ClinPred
0.46
T
GERP RS
3.6
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.73
gMVP
0.68

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: rs149599017; hg19: chr19-6380350; COSMIC: COSV55532035; COSMIC: COSV55532035; API