Variant 13-45151730-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_004128.3(GTF2F2):c.203T>C(p.Ile68Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000903 in 1,606,490 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000096 ( 0 hom. )

Consequence

GTF2F2
NM_004128.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.64

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]

GTF2F2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.23879898).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
GTF2F2	NM_004128.3 linkuse as main transcript	c.203T>C	p.Ile68Thr	missense_variant	4/8	ENST00000340473.8	NP_004119.1
GTF2F2	XM_011535052.4 linkuse as main transcript	c.203T>C	p.Ile68Thr	missense_variant	4/9		XP_011533354.1
GTF2F2	XM_011535053.4 linkuse as main transcript	c.203T>C	p.Ile68Thr	missense_variant	4/6		XP_011533355.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GTF2F2	ENST00000340473.8 linkuse as main transcript	c.203T>C	p.Ile68Thr	missense_variant	4/8	1	NM_004128.3	ENSP00000340823	P1
GTF2F2	ENST00000706694.1 linkuse as main transcript	c.32T>C	p.Ile11Thr	missense_variant, NMD_transcript_variant	1/6			ENSP00000516507

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152140

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000735

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000401

AC:

AN:

249076

Hom.:

AF XY:

0.0000371

AC XY:

AN XY:

134634

show subpopulations

Gnomad AFR exome

AF:

0.0000618

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000708

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.0000963

AC:

140

AN:

1454350

Hom.:

Cov.:

AF XY:

0.0000912

AC XY:

AN XY:

723832

show subpopulations

Gnomad4 AFR exome

AF:

0.0000300

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.0000384

Gnomad4 EAS exome

AF:

0.0000759

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000118

Gnomad4 OTH exome

AF:

0.0000832

GnomAD4 genome

AF:

0.0000329

AC:

AN:

152140

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74328

show subpopulations

Gnomad4 AFR

AF:

0.00

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:

0.0000735

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000761

Hom.:

Bravo

AF:

0.0000264

ExAC

AF:

0.0000412

AC:

EpiCase

AF:

0.0000546

EpiControl

AF:

0.000298

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

Jul 12, 2023

The c.203T>C (p.I68T) alteration is located in exon 4 (coding exon 4) of the GTF2F2 gene. This alteration results from a T to C substitution at nucleotide position 203, causing the isoleucine (I) at amino acid position 68 to be replaced by a threonine (T). 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

0.068

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.24

CADD

Benign

DANN

Benign

0.88

DEOGEN2

Benign

0.060

Eigen

Benign

-0.24

Eigen_PC

Benign

-0.038

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.84

M_CAP

Benign

0.0035

MetaRNN

Benign

0.24

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.77

PROVEAN

Benign

0.11

REVEL

Benign

0.090

Sift

Benign

0.68

Sift4G

Benign

0.67

Polyphen

0.0010

Vest4

0.59

MVP

0.54

MPC

0.66

ClinPred

0.064

GERP RS

4.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.27

gMVP

0.43

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over