dbSNP rs9245: TXNIP:c.-222A>G (chr1-145996488-T-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_006472.6(TXNIP):c.-222A>G 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 0.00000658 in 152,002 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.0000066 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

TXNIP
NM_006472.6 5_prime_UTR_premature_start_codon_gain

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.67

Publications

22 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: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (Cadd=0.927).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006472.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TXNIP	NM_006472.6	MANE Select	c.-222A>G		5_prime_UTR_premature_start_codon_gain	Exon 1 of 8	NP_006463.3
	TXNIP	NM_006472.6	MANE Select	c.-222A>G		5_prime_UTR	Exon 1 of 8	NP_006463.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TXNIP	ENST00000582401.6	TSL:1 MANE Select	c.-222A>G		5_prime_UTR_premature_start_codon_gain	Exon 1 of 8	ENSP00000462521.1
	TXNIP	ENST00000582401.6	TSL:1 MANE Select	c.-222A>G		5_prime_UTR	Exon 1 of 8	ENSP00000462521.1

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

152002

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

314468

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

166334

African (AFR)

AF:

0.00

AC:

AN:

9316

American (AMR)

AF:

0.00

AC:

AN:

9450

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

9870

East Asian (EAS)

AF:

0.00

AC:

AN:

19432

South Asian (SAS)

AF:

0.00

AC:

AN:

34316

European-Finnish (FIN)

AF:

0.00

AC:

AN:

16106

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1434

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

196634

Other (OTH)

AF:

0.00

AC:

AN:

17910

GnomAD4 genome

AF:

0.00000658

AC:

AN:

152002

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74230

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41358

American (AMR)

AF:

0.00

AC:

AN:

15240

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5174

South Asian (SAS)

AF:

0.000207

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10576

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68034

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00

Hom.:

30213

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

CADD

Benign

0.93

(source)

PhyloP100

-1.7

PromoterAI

0.014

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

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