Variant chr1-145994128-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_006472.6(TXNIP):c.1028G>A(p.Arg343Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00118 in 1,614,082 control chromosomes in the GnomAD database, including 30 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00065 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0012 ( 29 hom. )

Consequence

TXNIP
NM_006472.6 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 5.01

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.06283116).

BP6

Variant 1-145994128-C-T is Benign according to our data. Variant chr1-145994128-C-T is described in ClinVar as [Benign]. Clinvar id is 726271.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4_exome allele frequency = 0.00124 (1812/1461890) while in subpopulation SAS AF= 0.0171 (1478/86258). AF 95% confidence interval is 0.0164. There are 29 homozygotes in gnomad4_exome. There are 1303 alleles in male gnomad4_exome subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 29 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TXNIP	NM_006472.6 linkuse as main transcript	c.1028G>A	p.Arg343Gln	missense_variant	7/8	ENST00000582401.6
TXNIP	NM_001313972.2 linkuse as main transcript	c.863G>A	p.Arg288Gln	missense_variant	6/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TXNIP	ENST00000582401.6 linkuse as main transcript	c.1028G>A	p.Arg343Gln	missense_variant	7/8	1	NM_006472.6	P1	Q9H3M7-1
TXNIP	ENST00000425134.2 linkuse as main transcript	c.863G>A	p.Arg288Gln	missense_variant	6/7	2			Q9H3M7-2
TXNIP	ENST00000486597.1 linkuse as main transcript	n.89G>A		non_coding_transcript_exon_variant	1/2	2
TXNIP	ENST00000488537.1 linkuse as main transcript	n.902G>A		non_coding_transcript_exon_variant	3/3	5

Frequencies

GnomAD3 genomes

AF:

0.000658

AC:

100

AN:

152074

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000725

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00212

Gnomad SAS

AF:

0.0133

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00227

AC:

570

AN:

251450

Hom.:

AF XY:

0.00305

AC XY:

415

AN XY:

135896

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000578

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00130

Gnomad SAS exome

AF:

0.0163

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000290

Gnomad OTH exome

AF:

0.00196

GnomAD4 exome

AF:

0.00124

AC:

1812

AN:

1461890

Hom.:

Cov.:

AF XY:

0.00179

AC XY:

1303

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.000119

Gnomad4 AMR exome

AF:

0.000112

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00139

Gnomad4 SAS exome

AF:

0.0171

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000166

Gnomad4 OTH exome

AF:

0.00121

GnomAD4 genome

AF:

0.000650

AC:

AN:

152192

Hom.:

Cov.:

AF XY:

0.000847

AC XY:

AN XY:

74406

show subpopulations

Gnomad4 AFR

AF:

0.0000723

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00212

Gnomad4 SAS

AF:

0.0131

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000459

Hom.:

Bravo

AF:

0.000332

Asia WGS

AF:

0.00375

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

Jun 06, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_noAF

Benign

-0.21

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.29

T;.

LIST_S2

Uncertain

0.90

D;D

MetaRNN

Benign

0.063

T;T

PROVEAN

Benign

-0.57

.;N

Sift

Benign

0.073

.;T

Sift4G

Benign

0.15

T;T

Vest4

0.53

RBP_binding_hub_radar

1.0

RBP_regulation_power_radar

2.1

gMVP

0.82

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