Genetic Variant TXNIP:c.*402C>T (chr1-145993449-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_006472.6(TXNIP):c.*402C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.193 in 164,592 control chromosomes in the GnomAD database, including 6,451 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 0.20 ( 6315 hom., cov: 32)

Exomes 𝑓: 0.11 ( 136 hom. )

Consequence

TXNIP
NM_006472.6 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.00700

Publications

28 publications found

Variant links:

Genes affected

TXNIP (HGNC:16952): (thioredoxin interacting protein) This gene encodes a thioredoxin-binding protein that is a member of the alpha arrestin protein family. Thioredoxin is a thiol-oxidoreductase that is a major regulator of cellular redox signaling which protects cells from oxidative stress. This protein inhibits the antioxidative function of thioredoxin resulting in the accumulation of reactive oxygen species and cellular stress. This protein also functions as a regulator of cellular metabolism and of endoplasmic reticulum (ER) stress. This protein may also function as a tumor suppressor. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Sep 2015]

TXNIP links:

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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=-0.79).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.515 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TXNIP	NM_006472.6 link	c.*402C>T		3_prime_UTR_variant	Exon 8 of 8	ENST00000582401.6	NP_006463.3	Q9H3M7-1
TXNIP	NM_001313972.2 link	c.*402C>T		3_prime_UTR_variant	Exon 7 of 7		NP_001300901.1	Q9H3M7-2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
TXNIP	ENST00000582401.6 link	c.*402C>T	3_prime_UTR_variant	Exon 8 of 8	1	NM_006472.6	ENSP00000462521.1	Q9H3M7-1
TXNIP	ENST00000486597.1 link	n.*130C>T	downstream_gene_variant		2
TXNIP	ENST00000488537.1 link	n.*72C>T	downstream_gene_variant		5

Frequencies

GnomAD3 genomes

AF:

0.199

AC:

30277

AN:

151790

Hom.:

6281

Cov.:

show subpopulations

Gnomad AFR

AF:

0.521

Gnomad AMI

AF:

0.0603

Gnomad AMR

AF:

0.191

Gnomad ASJ

AF:

0.0507

Gnomad EAS

AF:

0.182

Gnomad SAS

AF:

0.145

Gnomad FIN

AF:

0.0662

Gnomad MID

AF:

0.0854

Gnomad NFE

AF:

0.0435

Gnomad OTH

AF:

0.158

GnomAD4 exome

AF:

0.106

AC:

1339

AN:

12684

Hom.:

136

Cov.:

AF XY:

0.108

AC XY:

736

AN XY:

6794

show subpopulations

African (AFR)

AF:

0.505

AC:

108

AN:

214

American (AMR)

AF:

0.203

AC:

401

AN:

1980

Ashkenazi Jewish (ASJ)

AF:

0.0772

AC:

AN:

324

East Asian (EAS)

AF:

0.268

AC:

153

AN:

570

South Asian (SAS)

AF:

0.131

AC:

245

AN:

1866

European-Finnish (FIN)

AF:

0.0857

AC:

AN:

210

Middle Eastern (MID)

AF:

0.125

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0445

AC:

306

AN:

6882

Other (OTH)

AF:

0.130

AC:

AN:

598

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.527

Heterozygous variant carriers

108

161

215

269

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.200

AC:

30372

AN:

151908

Hom.:

6315

Cov.:

AF XY:

0.200

AC XY:

14845

AN XY:

74254

show subpopulations

African (AFR)

AF:

0.521

AC:

21567

AN:

41386

American (AMR)

AF:

0.192

AC:

2926

AN:

15246

Ashkenazi Jewish (ASJ)

AF:

0.0507

AC:

176

AN:

3470

East Asian (EAS)

AF:

0.181

AC:

936

AN:

5162

South Asian (SAS)

AF:

0.144

AC:

693

AN:

4814

European-Finnish (FIN)

AF:

0.0662

AC:

698

AN:

10538

Middle Eastern (MID)

AF:

0.0850

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0435

AC:

2956

AN:

67976

Other (OTH)

AF:

0.161

AC:

340

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

917

1834

2751

3668

4585

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0871

Hom.:

2069

Bravo

AF:

0.224

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

3.5

(source)

PhyloP100

0.0070

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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

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1-145993449-G-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over