1-145994078-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 5.48

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 -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 GnomAd at 3 AR gene

Transcripts

RefSeq

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

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.000920 AC: 140 AN: 152138 Hom.: 3 Cov.: 32

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.: 1 AF XY: 0.00104 AC XY: 141 AN XY: 135882

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.: 4 Cov.: 32 AF XY: 0.00128 AC XY: 928 AN XY: 727248

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.: 3 Cov.: 32 AF XY: 0.000725 AC XY: 54 AN XY: 74456

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.: 1

Bravo AF: 0.000880

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

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	24
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

Other links and lift over

dbSNP: rs150987946; hg19: chr1-145440991;