1-145993449-G-T

Variant names:

• chr1-145993449-G-T
• rs7211
• NM_006472.6:c.*402C>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_006472.6(TXNIP):​c.*402C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000304 in 164,644 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 0.00032 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000079 (0 hom.)
• Consequence: TXNIP NM_006472.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00700
• Publications: 28 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).

Transcripts

RefSeq

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

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.000323 AC: 49 AN: 151826 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00114

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000657

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000787 AC: 1 AN: 12700 Hom.: 0 Cov.: 0 AF XY: 0.000147 AC XY: 1 AN XY: 6804

African (AFR) AF: 0.00 AC: 0 AN: 216

American (AMR) AF: 0.00 AC: 0 AN: 1984

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 324

East Asian (EAS) AF: 0.00 AC: 0 AN: 572

South Asian (SAS) AF: 0.00 AC: 0 AN: 1866

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 210

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 40

European-Non Finnish (NFE) AF: 0.000145 AC: 1 AN: 6890

Other (OTH) AF: 0.00 AC: 0 AN: 598

GnomAD4 genome AF: 0.000322 AC: 49 AN: 151944 Hom.: 0 Cov.: 32 AF XY: 0.000256 AC XY: 19 AN XY: 74274

African (AFR) AF: 0.00113 AC: 47 AN: 41414

American (AMR) AF: 0.0000656 AC: 1 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5166

South Asian (SAS) AF: 0.00 AC: 0 AN: 4814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10538

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67980

Other (OTH) AF: 0.00 AC: 0 AN: 2110

Alfa AF: 0.00 Hom.: 2069

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.0
PhyloP100		0.0070

Splicing

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

Other links and lift over

dbSNP: rs7211; hg19: chr1-145441620;