Variant chr13-45267357-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_004128.3(GTF2F2):c.611A>T(p.Asp204Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000622 in 1,608,976 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

GTF2F2
NM_004128.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.88

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
GTF2F2	NM_004128.3 linkuse as main transcript	c.611A>T	p.Asp204Val	missense_variant	7/8	ENST00000340473.8	NP_004119.1
GTF2F2	XM_011535052.4 linkuse as main transcript	c.689A>T	p.Asp230Val	missense_variant	8/9		XP_011533354.1
GTF2F2	XM_017020551.2 linkuse as main transcript	c.311A>T	p.Asp104Val	missense_variant	4/5		XP_016876040.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GTF2F2	ENST00000340473.8 linkuse as main transcript	c.611A>T	p.Asp204Val	missense_variant	7/8	1	NM_004128.3	ENSP00000340823	P1

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152190

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:

0.000578

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000161

AC:

AN:

248260

Hom.:

AF XY:

0.00000745

AC XY:

AN XY:

134208

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000164

Gnomad SAS exome

AF:

0.0000335

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000412

AC:

AN:

1456668

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

724876

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000126

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.02e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152308

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000579

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000151

ExAC

AF:

0.0000247

AC:

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 14, 2022

The c.611A>T (p.D204V) alteration is located in exon 7 (coding exon 7) of the GTF2F2 gene. This alteration results from a A to T substitution at nucleotide position 611, causing the aspartic acid (D) at amino acid position 204 to be replaced by a valine (V). 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

0.43

BayesDel_addAF

Pathogenic

0.24

BayesDel_noAF

Pathogenic

0.37

CADD

Uncertain

DANN

Benign

0.94

DEOGEN2

Benign

0.23

Eigen

Uncertain

0.32

Eigen_PC

Uncertain

0.41

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.96

M_CAP

Benign

0.050

MetaRNN

Uncertain

0.60

MetaSVM

Benign

-0.66

MutationAssessor

Uncertain

2.5

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.75

PROVEAN

Uncertain

-2.4

REVEL

Uncertain

0.56

Sift

Benign

0.29

Sift4G

Benign

0.31

Polyphen

0.42

Vest4

0.80

MutPred

0.36

Gain of catalytic residue at Q208 (P = 0.0026);

MVP

0.64

MPC

1.6

ClinPred

0.43

GERP RS

5.2

Varity_R

0.77

gMVP

0.64

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