13-45120684-C-T

Variant summary

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

The NM_004128.3(GTF2F2):​c.29C>T​(p.Thr10Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000142 in 1,409,362 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: 0.0000014 ( 0 hom. )

Consequence

GTF2F2
NM_004128.3 missense

Scores

1
11
7

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.85
Variant links:
Genes affected
GTF2F2 (HGNC:4653): (general transcription factor IIF subunit 2) Predicted to enable RNA polymerase II general transcription initiation factor activity. Involved in transcription by RNA polymerase II. Located in microtubule cytoskeleton and nucleoplasm. Part of transcription preinitiation complex. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

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=0.39259925).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GTF2F2NM_004128.3 linkc.29C>T p.Thr10Ile missense_variant Exon 1 of 8 ENST00000340473.8 NP_004119.1 P13984A0A024RDU9
GTF2F2XM_011535052.4 linkc.29C>T p.Thr10Ile missense_variant Exon 1 of 9 XP_011533354.1
GTF2F2XM_011535053.4 linkc.29C>T p.Thr10Ile missense_variant Exon 1 of 6 XP_011533355.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
GTF2F2ENST00000340473.8 linkc.29C>T p.Thr10Ile missense_variant Exon 1 of 8 1 NM_004128.3 ENSP00000340823.6 P13984

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000142
AC:
2
AN:
1409362
Hom.:
0
Cov.:
30
AF XY:
0.00
AC XY:
0
AN XY:
695968
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000125
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.0000171
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
Dec 20, 2022
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.29C>T (p.T10I) alteration is located in exon 1 (coding exon 1) of the GTF2F2 gene. This alteration results from a C to T substitution at nucleotide position 29, causing the threonine (T) at amino acid position 10 to be replaced by an isoleucine (I). 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
0.48
BayesDel_addAF
Uncertain
0.067
T
BayesDel_noAF
Benign
-0.14
CADD
Pathogenic
27
DANN
Uncertain
1.0
DEOGEN2
Benign
0.26
T
Eigen
Uncertain
0.47
Eigen_PC
Uncertain
0.51
FATHMM_MKL
Uncertain
0.93
D
LIST_S2
Uncertain
0.90
D
M_CAP
Benign
0.025
T
MetaRNN
Benign
0.39
T
MetaSVM
Benign
-0.58
T
MutationAssessor
Uncertain
2.1
M
PrimateAI
Pathogenic
0.85
D
PROVEAN
Uncertain
-2.5
N
REVEL
Benign
0.14
Sift
Uncertain
0.0050
D
Sift4G
Uncertain
0.045
D
Polyphen
0.83
P
Vest4
0.42
MutPred
0.54
Gain of catalytic residue at N15 (P = 0.0023);
MVP
0.67
MPC
1.0
ClinPred
0.98
D
GERP RS
5.2
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
2.0
Varity_R
0.71
gMVP
0.48

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: chr13-45694819; API