Variant 13-45151783-C-G 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.256C>G(p.Gln86Glu) variant causes a missense change. The variant allele was found at a frequency of 0.0000479 in 1,585,466 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 0.00026 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000025 ( 0 hom. )

Consequence

GTF2F2
NM_004128.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.26

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:

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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=0.24816355).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
GTF2F2	NM_004128.3 linkuse as main transcript	c.256C>G	p.Gln86Glu	missense_variant	4/8	ENST00000340473.8	NP_004119.1
GTF2F2	XM_011535052.4 linkuse as main transcript	c.256C>G	p.Gln86Glu	missense_variant	4/9		XP_011533354.1
GTF2F2	XM_011535053.4 linkuse as main transcript	c.256C>G	p.Gln86Glu	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.256C>G	p.Gln86Glu	missense_variant	4/8	1	NM_004128.3	ENSP00000340823	P1
GTF2F2	ENST00000706694.1 linkuse as main transcript	c.85C>G	p.Gln29Glu	missense_variant, NMD_transcript_variant	1/6			ENSP00000516507

Frequencies

GnomAD3 genomes

AF:

0.000263

AC:

AN:

151918

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000967

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:

0.0000581

AC:

AN:

241072

Hom.:

AF XY:

0.0000384

AC XY:

AN XY:

130344

show subpopulations

Gnomad AFR exome

AF:

0.000879

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000251

AC:

AN:

1433548

Hom.:

Cov.:

AF XY:

0.0000224

AC XY:

AN XY:

714284

show subpopulations

Gnomad4 AFR exome

AF:

0.00107

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000169

GnomAD4 genome

AF:

0.000263

AC:

AN:

151918

Hom.:

Cov.:

AF XY:

0.000216

AC XY:

AN XY:

74176

show subpopulations

Gnomad4 AFR

AF:

0.000967

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

Alfa

AF:

0.0000452

Hom.:

Bravo

AF:

0.000246

ESP6500AA

AF:

0.00113

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000824

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

May 20, 2024

The c.256C>G (p.Q86E) alteration is located in exon 4 (coding exon 4) of the GTF2F2 gene. This alteration results from a C to G substitution at nucleotide position 256, causing the glutamine (Q) at amino acid position 86 to be replaced by a glutamic acid (E). 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

0.18

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.18

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.12

Eigen

Uncertain

0.26

Eigen_PC

Uncertain

0.34

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.95

M_CAP

Benign

0.0082

MetaRNN

Benign

0.25

MetaSVM

Benign

-0.74

MutationAssessor

Uncertain

2.6

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.70

PROVEAN

Benign

-0.99

REVEL

Benign

0.14

Sift

Benign

0.059

Sift4G

Benign

0.44

Polyphen

0.67

Vest4

0.77

MVP

0.44

MPC

1.1

ClinPred

0.16

GERP RS

5.1

Varity_R

0.48

gMVP

0.60

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