1-145996488-T-G

Variant names:

• chr1-145996488-T-G
• rs9245
• NM_006472.6:c.-222A>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 22 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: Benign. The variant received -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.

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>C		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>C		5_prime_UTR	Exon 1 of 8	ENSP00000462521.1

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

African (AFR) AF: 0.942 AC: 8768 AN: 9312

American (AMR) AF: 0.930 AC: 8778 AN: 9438

Ashkenazi Jewish (ASJ) AF: 0.820 AC: 8073 AN: 9844

East Asian (EAS) AF: 0.765 AC: 14819 AN: 19362

South Asian (SAS) AF: 0.877 AC: 30050 AN: 34268

European-Finnish (FIN) AF: 0.946 AC: 15220 AN: 16088

Middle Eastern (MID) AF: 0.808 AC: 1159 AN: 1434

European-Non Finnish (NFE) AF: 0.913 AC: 179344 AN: 196386

Other (OTH) AF: 0.897 AC: 16051 AN: 17894

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

African (AFR) AF: 0.941 AC: 39016 AN: 41476

American (AMR) AF: 0.922 AC: 14067 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.817 AC: 2834 AN: 3468

East Asian (EAS) AF: 0.785 AC: 4049 AN: 5160

South Asian (SAS) AF: 0.879 AC: 4242 AN: 4828

European-Finnish (FIN) AF: 0.951 AC: 10055 AN: 10576

Middle Eastern (MID) AF: 0.793 AC: 233 AN: 294

European-Non Finnish (NFE) AF: 0.914 AC: 62151 AN: 68018

Other (OTH) AF: 0.894 AC: 1889 AN: 2112

Alfa AF: 0.910 Hom.: 30213

Bravo AF: 0.915

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
CADD	Benign	0.75
PhyloP100		-1.7
PromoterAI		0.059	Neutral
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

Other links and lift over

dbSNP: rs9245;