19-6380930-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_002096.3(GTF2F1):​c.1205G>A​(p.Arg402Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000431 in 1,576,204 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R402W) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00014 ( 1 hom., cov: 32)
Exomes 𝑓: 0.000033 ( 0 hom. )

Consequence

GTF2F1
NM_002096.3 missense

Scores

5
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.14
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 Benign. Variant got -8 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.050388306).
BS2
High AC in GnomAd4 at 21 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GTF2F1NM_002096.3 linkc.1205G>A p.Arg402Gln missense_variant Exon 11 of 13 ENST00000394456.10 NP_002087.2 P35269
GTF2F1XM_047438710.1 linkc.1232G>A p.Arg411Gln missense_variant Exon 10 of 12 XP_047294666.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
GTF2F1ENST00000394456.10 linkc.1205G>A p.Arg402Gln missense_variant Exon 11 of 13 1 NM_002096.3 ENSP00000377969.3 P35269
GTF2F1ENST00000593678.5 linkc.953G>A p.Arg318Gln missense_variant Exon 8 of 10 2 ENSP00000469091.1 M0QXD6
GTF2F1ENST00000594213.5 linkn.572G>A non_coding_transcript_exon_variant Exon 4 of 6 3
GTF2F1ENST00000594965.1 linkn.523G>A non_coding_transcript_exon_variant Exon 4 of 6 3

Frequencies

GnomAD3 genomes
AF:
0.000138
AC:
21
AN:
152198
Hom.:
1
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000386
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000196
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:
0.0000147
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.0000626
AC:
12
AN:
191626
Hom.:
0
AF XY:
0.0000575
AC XY:
6
AN XY:
104280
show subpopulations
Gnomad AFR exome
AF:
0.000435
Gnomad AMR exome
AF:
0.0000697
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000384
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000492
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000330
AC:
47
AN:
1423888
Hom.:
0
Cov.:
33
AF XY:
0.0000298
AC XY:
21
AN XY:
705732
show subpopulations
Gnomad4 AFR exome
AF:
0.000184
Gnomad4 AMR exome
AF:
0.0000755
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000243
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000265
Gnomad4 OTH exome
AF:
0.000119
GnomAD4 genome
AF:
0.000138
AC:
21
AN:
152316
Hom.:
1
Cov.:
32
AF XY:
0.000134
AC XY:
10
AN XY:
74488
show subpopulations
Gnomad4 AFR
AF:
0.000385
Gnomad4 AMR
AF:
0.000196
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.000473
Alfa
AF:
0.0000434
Hom.:
0
Bravo
AF:
0.000121
ESP6500AA
AF:
0.000229
AC:
1
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.0000666
AC:
8

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Oct 29, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1205G>A (p.R402Q) alteration is located in exon 11 (coding exon 11) of the GTF2F1 gene. This alteration results from a G to A substitution at nucleotide position 1205, causing the arginine (R) at amino acid position 402 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
Benign
0.13
BayesDel_addAF
Benign
-0.35
T
BayesDel_noAF
Benign
-0.43
CADD
Benign
21
DANN
Uncertain
1.0
DEOGEN2
Benign
0.071
T;T
Eigen
Benign
-0.24
Eigen_PC
Benign
-0.24
FATHMM_MKL
Uncertain
0.89
D
LIST_S2
Uncertain
0.92
D;D
M_CAP
Uncertain
0.085
D
MetaRNN
Benign
0.050
T;T
MetaSVM
Benign
-0.89
T
MutationAssessor
Benign
1.6
L;.
PrimateAI
Uncertain
0.50
T
PROVEAN
Benign
-1.1
N;.
REVEL
Benign
0.090
Sift
Benign
0.24
T;.
Sift4G
Benign
0.41
T;T
Polyphen
0.039
B;.
Vest4
0.23
MVP
0.63
MPC
0.68
ClinPred
0.068
T
GERP RS
3.4
Varity_R
0.078
gMVP
0.41

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs370397042; hg19: chr19-6380941; API