1-145996488-T-G

Position:

• chr1-145996488-T-G

Variant summary

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

The NM_006472.6(TXNIP):​c.-222A>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.904 in 466,122 control chromosomes in the GnomAD database, including 191,172 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 0.92 (63976 hom., cov: 31)
  • Exomes 𝑓: 0.90 (127196 hom.)
• Consequence: TXNIP NM_006472.6 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.67

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=0.748).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.933 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TXNIP	NM_006472.6	c.-222A>C		5_prime_UTR_variant	1/8	ENST00000582401.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TXNIP	ENST00000582401.6	c.-222A>C		5_prime_UTR_variant	1/8	1	NM_006472.6	P1

Frequencies

GnomAD3 genomes AF: 0.916 AC: 139225 AN: 151978 Hom.: 63919 Cov.: 31

Gnomad AFR AF: 0.941

Gnomad AMI AF: 0.882

Gnomad AMR AF: 0.922

Gnomad ASJ AF: 0.817

Gnomad EAS AF: 0.785

Gnomad SAS AF: 0.880

Gnomad FIN AF: 0.951

Gnomad MID AF: 0.794

Gnomad NFE AF: 0.914

Gnomad OTH AF: 0.893

GnomAD4 exome AF: 0.899 AC: 282262 AN: 314026 Hom.: 127196 Cov.: 4 AF XY: 0.896 AC XY: 148892 AN XY: 166090

Gnomad4 AFR exome AF: 0.942

Gnomad4 AMR exome AF: 0.930

Gnomad4 ASJ exome AF: 0.820

Gnomad4 EAS exome AF: 0.765

Gnomad4 SAS exome AF: 0.877

Gnomad4 FIN exome AF: 0.946

Gnomad4 NFE exome AF: 0.913

Gnomad4 OTH exome AF: 0.897

GnomAD4 genome AF: 0.916 AC: 139339 AN: 152096 Hom.: 63976 Cov.: 31 AF XY: 0.915 AC XY: 68039 AN XY: 74344

Gnomad4 AFR AF: 0.941

Gnomad4 AMR AF: 0.922

Gnomad4 ASJ AF: 0.817

Gnomad4 EAS AF: 0.785

Gnomad4 SAS AF: 0.879

Gnomad4 FIN AF: 0.951

Gnomad4 NFE AF: 0.914

Gnomad4 OTH AF: 0.894

Alfa AF: 0.909 Hom.: 29876

Bravo AF: 0.915

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
CADD	Benign	0.75
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

LitVar

Other links and lift over

dbSNP: rs9245; hg19: -;