Variant chr1-145994078-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_006472.6(TXNIP):c.1078G>A(p.Asp360Asn) variant causes a missense change. The variant allele was found at a frequency of 0.0013 in 1,614,148 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00092 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0013 ( 4 hom. )

Consequence

TXNIP
NM_006472.6 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 5.48

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 made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.05775684).

BP6

Variant 1-145994078-C-T is Benign according to our data. Variant chr1-145994078-C-T is described in ClinVar as [Benign]. Clinvar id is 777922.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TXNIP	NM_006472.6 linkuse as main transcript	c.1078G>A	p.Asp360Asn	missense_variant	7/8	ENST00000582401.6
TXNIP	NM_001313972.2 linkuse as main transcript	c.913G>A	p.Asp305Asn	missense_variant	6/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TXNIP	ENST00000582401.6 linkuse as main transcript	c.1078G>A	p.Asp360Asn	missense_variant	7/8	1	NM_006472.6	P1	Q9H3M7-1
TXNIP	ENST00000425134.2 linkuse as main transcript	c.913G>A	p.Asp305Asn	missense_variant	6/7	2			Q9H3M7-2
TXNIP	ENST00000486597.1 linkuse as main transcript	n.139G>A		non_coding_transcript_exon_variant	1/2	2
TXNIP	ENST00000488537.1 linkuse as main transcript	n.952G>A		non_coding_transcript_exon_variant	3/3	5

Frequencies

GnomAD3 genomes

AF:

0.000920

AC:

140

AN:

152138

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000410

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000524

Gnomad ASJ

AF:

0.0141

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000941

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.00110

AC:

277

AN:

251428

Hom.:

AF XY:

0.00104

AC XY:

141

AN XY:

135882

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.000116

Gnomad ASJ exome

AF:

0.0146

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000994

Gnomad OTH exome

AF:

0.00196

GnomAD4 exome

AF:

0.00134

AC:

1959

AN:

1461892

Hom.:

Cov.:

AF XY:

0.00128

AC XY:

928

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.000149

Gnomad4 AMR exome

AF:

0.000246

Gnomad4 ASJ exome

AF:

0.0139

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000562

Gnomad4 NFE exome

AF:

0.00133

Gnomad4 OTH exome

AF:

0.00167

GnomAD4 genome

AF:

0.000920

AC:

140

AN:

152256

Hom.:

Cov.:

AF XY:

0.000725

AC XY:

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.000409

Gnomad4 AMR

AF:

0.000523

Gnomad4 ASJ

AF:

0.0141

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000941

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.00179

Hom.:

Bravo

AF:

0.000880

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jul 31, 2018

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Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_noAF

Pathogenic

0.31

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.33

T;.

LIST_S2

Uncertain

0.90

D;D

MetaRNN

Benign

0.058

T;T

Sift4G

Benign

0.20

T;T

Vest4

0.56

gMVP

0.73

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over