Genetic Variant NM_006472.6:c.*1035C>G (chr1-145992816-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0980

Publications

20 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: Benign. The variant received -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.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TXNIP	NM_006472.6	MANE Select	c.*1035C>G		3_prime_UTR	Exon 8 of 8	NP_006463.3
	TXNIP	NM_001313972.2		c.*1035C>G		3_prime_UTR	Exon 7 of 7	NP_001300901.1	Q9H3M7-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TXNIP	ENST00000582401.6	TSL:1 MANE Select	c.*1035C>G	3_prime_UTR	Exon 8 of 8	ENSP00000462521.1	Q9H3M7-1
TXNIP	ENST00000883755.1		c.*1035C>G	3_prime_UTR	Exon 8 of 8	ENSP00000553814.1
TXNIP	ENST00000883753.1		c.*1035C>G	3_prime_UTR	Exon 8 of 8	ENSP00000553812.1

Frequencies

GnomAD3 genomes

AF:

0.153

AC:

23223

AN:

151982

Hom.:

3253

Cov.:

show subpopulations

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:

AN:

466

Hom.:

Cov.:

AF XY:

0.0621

AC XY:

AN XY:

290

show subpopulations

African (AFR)

AF:

1.00

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.500

AC:

AN:

South Asian (SAS)

AF:

0.500

AC:

AN:

European-Finnish (FIN)

AF:

0.0537

AC:

AN:

428

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0769

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.153

AC:

23280

AN:

152100

Hom.:

3270

Cov.:

AF XY:

0.155

AC XY:

11497

AN XY:

74374

show subpopulations

African (AFR)

AF:

0.362

AC:

15004

AN:

41430

American (AMR)

AF:

0.173

AC:

2643

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.0473

AC:

164

AN:

3470

East Asian (EAS)

AF:

0.177

AC:

916

AN:

5184

South Asian (SAS)

AF:

0.132

AC:

638

AN:

4824

European-Finnish (FIN)

AF:

0.0645

AC:

683

AN:

10592

Middle Eastern (MID)

AF:

0.0884

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0423

AC:

2875

AN:

68012

Other (OTH)

AF:

0.132

AC:

278

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

884

1768

2652

3536

4420

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

216

432

648

864

1080

<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:

0.0224

Hom.:

Bravo

AF:

0.171

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

CADD

Benign

1.1

(source)

PhyloP100

-0.098

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

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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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over