Variant chr14-81192567-C-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_015859.4(GTF2A1):c.885G>T(p.Glu295Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000245 in 1,613,176 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00022 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00025 ( 0 hom. )

Consequence

GTF2A1
NM_015859.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.294

Variant links:

Genes affected

GTF2A1 (HGNC:4646): (general transcription factor IIA subunit 1) Accurate transcription initiation on TATA-containing class II genes involves the ordered assembly of RNA polymerase II (POLR2A; MIM 180660) and several general initiation factors (summarized by DeJong and Roeder, 1993 [PubMed 8224848]). One of these factors is TFIIA, which when purified from HeLa extracts consists of 35-, 19-, and 12-kD subunits.[supplied by OMIM, Jul 2010]

GTF2A1 links:

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=0.06508139).

BS2

High AC in GnomAd4 at 33 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
GTF2A1	NM_015859.4 linkuse as main transcript	c.885G>T	p.Glu295Asp	missense_variant	7/9	ENST00000553612.6	NP_056943.1
GTF2A1	NM_201595.3 linkuse as main transcript	c.768G>T	p.Glu256Asp	missense_variant	7/9		NP_963889.1
GTF2A1	NM_001278940.2 linkuse as main transcript	c.735G>T	p.Glu245Asp	missense_variant	8/10		NP_001265869.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GTF2A1	ENST00000553612.6 linkuse as main transcript	c.885G>T	p.Glu295Asp	missense_variant	7/9	1	NM_015859.4	ENSP00000452454	P1	P52655-1
GTF2A1	ENST00000434192.2 linkuse as main transcript	c.768G>T	p.Glu256Asp	missense_variant	7/9	1		ENSP00000409492		P52655-2
GTF2A1	ENST00000298173.7 linkuse as main transcript	c.*772G>T		3_prime_UTR_variant, NMD_transcript_variant	8/10	2		ENSP00000298173

Frequencies

GnomAD3 genomes

AF:

0.000217

AC:

AN:

152156

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

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:

0.000367

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000283

AC:

AN:

251100

Hom.:

AF XY:

0.000265

AC XY:

AN XY:

135706

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.000203

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000463

Gnomad NFE exome

AF:

0.000537

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000248

AC:

363

AN:

1461020

Hom.:

Cov.:

AF XY:

0.000252

AC XY:

183

AN XY:

726842

show subpopulations

Gnomad4 AFR exome

AF:

0.000120

Gnomad4 AMR exome

AF:

0.000224

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000562

Gnomad4 NFE exome

AF:

0.000303

Gnomad4 OTH exome

AF:

0.000133

GnomAD4 genome

AF:

0.000217

AC:

AN:

152156

Hom.:

Cov.:

AF XY:

0.000175

AC XY:

AN XY:

74332

show subpopulations

Gnomad4 AFR

AF:

0.0000483

Gnomad4 AMR

AF:

0.000393

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000367

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000421

Hom.:

Bravo

AF:

0.000329

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000305

AC:

EpiCase

AF:

0.000436

EpiControl

AF:

0.000889

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

Jun 17, 2024

The c.885G>T (p.E295D) alteration is located in exon 7 (coding exon 7) of the GTF2A1 gene. This alteration results from a G to T substitution at nucleotide position 885, causing the glutamic acid (E) at amino acid position 295 to be replaced by an aspartic acid (D). 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

0.067

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.53

CADD

Benign

9.4

DANN

Uncertain

0.98

DEOGEN2

Benign

0.092

T;.

Eigen

Benign

-0.34

Eigen_PC

Benign

-0.38

FATHMM_MKL

Benign

0.73

LIST_S2

Uncertain

0.89

D;D

M_CAP

Benign

0.011

MetaRNN

Benign

0.065

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.82

L;.

MutationTaster

Benign

0.98

D;D

PrimateAI

Uncertain

0.68

PROVEAN

Benign

-0.13

N;N

REVEL

Benign

0.16

Sift

Benign

0.19

T;T

Sift4G

Benign

0.61

T;T

Polyphen

0.98

D;.

Vest4

0.23

MutPred

0.36

Loss of helix (P = 0.079);.;

MVP

0.32

MPC

0.19

ClinPred

0.11

GERP RS

-2.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.8

Varity_R

0.038

gMVP

0.019

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