1-145992816-G-C

Position:

• chr1-145992816-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006472.6(TXNIP):​c.*1035C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.153 in 152,566 control chromosomes in the GnomAD database, including 3,272 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 0.15 (3270 hom., cov: 32)
  • Exomes 𝑓: 0.062 (2 hom.)
• Consequence: TXNIP NM_006472.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0980

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (Cadd=1.05).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.357 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TXNIP	NM_006472.6	c.*1035C>G		3_prime_UTR_variant	8/8	ENST00000582401.6	NP_006463.3
TXNIP	NM_001313972.2	c.*1035C>G		3_prime_UTR_variant	7/7		NP_001300901.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TXNIP	ENST00000582401	c.*1035C>G		3_prime_UTR_variant	8/8	1	NM_006472.6	ENSP00000462521.1

Frequencies

GnomAD3 genomes AF: 0.153 AC: 23223 AN: 151982 Hom.: 3253 Cov.: 32

Gnomad AFR AF: 0.362

Gnomad AMI AF: 0.0582

Gnomad AMR AF: 0.172

Gnomad ASJ AF: 0.0473

Gnomad EAS AF: 0.177

Gnomad SAS AF: 0.133

Gnomad FIN AF: 0.0645

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0423

Gnomad OTH AF: 0.128

GnomAD4 exome AF: 0.0622 AC: 29 AN: 466 Hom.: 2 Cov.: 0 AF XY: 0.0621 AC XY: 18 AN XY: 290

Gnomad4 AFR exome AF: 1.00

Gnomad4 EAS exome AF: 0.500

Gnomad4 SAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.0537

Gnomad4 NFE exome AF: 0.0769

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.153 AC: 23280 AN: 152100 Hom.: 3270 Cov.: 32 AF XY: 0.155 AC XY: 11497 AN XY: 74374

Gnomad4 AFR AF: 0.362

Gnomad4 AMR AF: 0.173

Gnomad4 ASJ AF: 0.0473

Gnomad4 EAS AF: 0.177

Gnomad4 SAS AF: 0.132

Gnomad4 FIN AF: 0.0645

Gnomad4 NFE AF: 0.0423

Gnomad4 OTH AF: 0.132

Alfa AF: 0.0224 Hom.: 18

Bravo AF: 0.171

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
CADD	Benign	1.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7212; hg19: -;