dbSNP rs5756208: TXN2:c.-65A>T (chr22-36481995-T-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000884008.1(TXN2):c.-65A>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.76 in 151,922 control chromosomes in the GnomAD database, including 44,786 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.76 ( 44760 hom., cov: 30)

Exomes 𝑓: 0.74 ( 26 hom. )

Consequence

TXN2
ENST00000884008.1 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.60

Publications

3 publications found

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 Gene-Disease associations (from GenCC):

combined oxidative phosphorylation defect type 29
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
combined oxidative phosphorylation deficiency 29
Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

TXN2 links:

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new If you want to explore the variant's impact on the transcript ENST00000884008.1, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.807 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000884008.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TXN2	ENST00000884008.1		c.-65A>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 4	ENSP00000554067.1
	TXN2	ENST00000884008.1		c.-65A>T		5_prime_UTR	Exon 1 of 4	ENSP00000554067.1

Frequencies

GnomAD3 genomes

AF:

0.760

AC:

115256

AN:

151712

Hom.:

44735

Cov.:

show subpopulations

Gnomad AFR

AF:

0.753

Gnomad AMI

AF:

0.868

Gnomad AMR

AF:

0.793

Gnomad ASJ

AF:

0.799

Gnomad EAS

AF:

0.260

Gnomad SAS

AF:

0.522

Gnomad FIN

AF:

0.723

Gnomad MID

AF:

0.791

Gnomad NFE

AF:

0.813

Gnomad OTH

AF:

0.765

GnomAD4 exome

AF:

0.739

AC:

AN:

Hom.:

Cov.:

AF XY:

0.697

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

1.00

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AF:

0.553

AC:

AN:

European-Finnish (FIN)

AF:

0.500

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.913

AC:

AN:

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.538

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.760

AC:

115335

AN:

151830

Hom.:

44760

Cov.:

AF XY:

0.751

AC XY:

55677

AN XY:

74186

show subpopulations

African (AFR)

AF:

0.753

AC:

31167

AN:

41388

American (AMR)

AF:

0.793

AC:

12102

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.799

AC:

2771

AN:

3468

East Asian (EAS)

AF:

0.260

AC:

1335

AN:

5132

South Asian (SAS)

AF:

0.522

AC:

2508

AN:

4808

European-Finnish (FIN)

AF:

0.723

AC:

7614

AN:

10526

Middle Eastern (MID)

AF:

0.793

AC:

233

AN:

294

European-Non Finnish (NFE)

AF:

0.813

AC:

55220

AN:

67934

Other (OTH)

AF:

0.760

AC:

1597

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1302

2603

3905

5206

6508

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

846

1692

2538

3384

4230

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.729

Hom.:

1690

Bravo

AF:

0.765

Asia WGS

AF:

0.420

AC:

1463

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

3.3

(source)

DANN

Benign

0.39

PhyloP100

-1.6

PromoterAI

-0.051

Neutral

(source)

Mutation Taster

=300/0

polymorphism (auto)

(source)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over