Variant 22-36476826-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_012473.4(TXN2):c.294G>A(p.Pro98=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00742 in 1,614,164 control chromosomes in the GnomAD database, including 68 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0059 ( 7 hom., cov: 32)

Exomes 𝑓: 0.0076 ( 61 hom. )

Consequence

TXN2
NM_012473.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -1.65

Variant links:

Genes affected

TXN2 (HGNC:17772): (thioredoxin 2) This nuclear gene encodes a mitochondrial member of the thioredoxin family, a group of small multifunctional redox-active proteins. The encoded protein may play important roles in the regulation of the mitochondrial membrane potential and in protection against oxidant-induced apoptosis. [provided by RefSeq, Jul 2008]

TXN2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.68).

BP6

Variant 22-36476826-C-T is Benign according to our data. Variant chr22-36476826-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 774540.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.65 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TXN2	NM_012473.4 linkuse as main transcript	c.294G>A	p.Pro98=	synonymous_variant	3/4	ENST00000216185.7
TXN2	XM_006724226.2 linkuse as main transcript	c.294G>A	p.Pro98=	synonymous_variant	3/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TXN2	ENST00000216185.7 linkuse as main transcript	c.294G>A	p.Pro98=	synonymous_variant	3/4	1	NM_012473.4	P1

Frequencies

GnomAD3 genomes

AF:

0.00586

AC:

892

AN:

152158

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00162

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00668

Gnomad ASJ

AF:

0.0141

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00394

Gnomad FIN

AF:

0.00226

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.00901

Gnomad OTH

AF:

0.00670

GnomAD3 exomes

AF:

0.00635

AC:

1597

AN:

251486

Hom.:

AF XY:

0.00645

AC XY:

877

AN XY:

135916

show subpopulations

Gnomad AFR exome

AF:

0.00105

Gnomad AMR exome

AF:

0.00593

Gnomad ASJ exome

AF:

0.0147

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00323

Gnomad FIN exome

AF:

0.00273

Gnomad NFE exome

AF:

0.00877

Gnomad OTH exome

AF:

0.0116

GnomAD4 exome

AF:

0.00758

AC:

11088

AN:

1461888

Hom.:

Cov.:

AF XY:

0.00754

AC XY:

5486

AN XY:

727244

show subpopulations

Gnomad4 AFR exome

AF:

0.00111

Gnomad4 AMR exome

AF:

0.00595

Gnomad4 ASJ exome

AF:

0.0156

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00342

Gnomad4 FIN exome

AF:

0.00333

Gnomad4 NFE exome

AF:

0.00839

Gnomad4 OTH exome

AF:

0.00780

GnomAD4 genome

AF:

0.00585

AC:

891

AN:

152276

Hom.:

Cov.:

AF XY:

0.00561

AC XY:

418

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.00161

Gnomad4 AMR

AF:

0.00667

Gnomad4 ASJ

AF:

0.0141

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00395

Gnomad4 FIN

AF:

0.00226

Gnomad4 NFE

AF:

0.00901

Gnomad4 OTH

AF:

0.00663

Alfa

AF:

0.00786

Hom.:

Bravo

AF:

0.00567

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.00845

EpiControl

AF:

0.00836

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jul 01, 2024	TXN2: BP4, BP7, BS1, BS2 -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 29, 2024	- -

Combined oxidative phosphorylation deficiency 29

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Oct 05, 2021

- -

TXN2-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Jan 13, 2020

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.68

CADD

Benign

3.0

DANN

Benign

0.56

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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