dbSNP rs3732533: TXNRD3:c.1367+23A>G (chr3-126622441-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_052883.3(TXNRD3):c.1367+23A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0697 in 1,505,454 control chromosomes in the GnomAD database, including 4,247 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 0.073 ( 468 hom., cov: 32)

Exomes 𝑓: 0.069 ( 3779 hom. )

Consequence

TXNRD3
NM_052883.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.923

Variant links:

Genes affected

TXNRD3 (HGNC:20667): (thioredoxin reductase 3) The protein encoded by this gene belongs to the pyridine nucleotide-disulfide oxidoreductase family, and is a member of the thioredoxin (Trx) system. Three thioredoxin reductase (TrxR) isozymes are found in mammals. TrxRs are selenocysteine-containing flavoenzymes, which reduce thioredoxins, as well as other substrates, and play a key role in redox homoeostasis. This gene encodes the third TrxR, which unlike the other two isozymes, contains an additional N-terminal glutaredoxin (Grx) domain, and shows highest expression in testis. The Grx domain allows this isozyme to participate in both Trx and glutathione systems. It functions as a homodimer containing FAD, and selenocysteine (Sec) at the active site. Sec is encoded by UGA codon that normally signals translation termination. The 3' UTRs of selenoprotein mRNAs contain a conserved stem-loop structure, the Sec insertion sequence (SECIS) element, which is necessary for the recognition of UGA as a Sec codon rather than as a stop signal. Alternatively spliced transcript variants have been found for this gene. Experimental evidence suggests the use of a non-AUG (CUG) codon as a translation initiation codon (PMID:20018845). [provided by RefSeq, Aug 2017]

TXNRD3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.187 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TXNRD3	NM_052883.3 link	c.1367+23A>G		intron_variant	Intron 11 of 15	ENST00000524230.9	NP_443115.1	Q86VQ6
TXNRD3	NM_001173513.3 link	c.1367+23A>G		intron_variant	Intron 11 of 14		NP_001166984.1	Q86VQ6B4DRZ5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TXNRD3	ENST00000524230.9 link	c.1367+23A>G		intron_variant	Intron 11 of 15	1	NM_052883.3	ENSP00000430031.4		Q86VQ6H0YBQ0
TXNRD3	ENST00000523403.3 link	c.1367+23A>G		intron_variant	Intron 11 of 14	2		ENSP00000429584.3		H0YBI6

Frequencies

GnomAD3 genomes

AF:

0.0730

AC:

11105

AN:

152128

Hom.:

463

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0602

Gnomad AMI

AF:

0.0263

Gnomad AMR

AF:

0.0843

Gnomad ASJ

AF:

0.0776

Gnomad EAS

AF:

0.197

Gnomad SAS

AF:

0.0870

Gnomad FIN

AF:

0.0843

Gnomad MID

AF:

0.0601

Gnomad NFE

AF:

0.0665

Gnomad OTH

AF:

0.0722

GnomAD3 exomes

AF:

0.0861

AC:

11218

AN:

130328

Hom.:

580

AF XY:

0.0856

AC XY:

6063

AN XY:

70832

show subpopulations

Gnomad AFR exome

AF:

0.0583

Gnomad AMR exome

AF:

0.0950

Gnomad ASJ exome

AF:

0.0734

Gnomad EAS exome

AF:

0.203

Gnomad SAS exome

AF:

0.0849

Gnomad FIN exome

AF:

0.0890

Gnomad NFE exome

AF:

0.0654

Gnomad OTH exome

AF:

0.0761

GnomAD4 exome

AF:

0.0694

AC:

93851

AN:

1353208

Hom.:

3779

Cov.:

AF XY:

0.0700

AC XY:

46857

AN XY:

669192

show subpopulations

Gnomad4 AFR exome

AF:

0.0578

Gnomad4 AMR exome

AF:

0.0956

Gnomad4 ASJ exome

AF:

0.0716

Gnomad4 EAS exome

AF:

0.186

Gnomad4 SAS exome

AF:

0.0855

Gnomad4 FIN exome

AF:

0.0895

Gnomad4 NFE exome

AF:

0.0629

Gnomad4 OTH exome

AF:

0.0732

GnomAD4 genome

AF:

0.0731

AC:

11126

AN:

152246

Hom.:

468

Cov.:

AF XY:

0.0745

AC XY:

5547

AN XY:

74436

show subpopulations

Gnomad4 AFR

AF:

0.0601

Gnomad4 AMR

AF:

0.0850

Gnomad4 ASJ

AF:

0.0776

Gnomad4 EAS

AF:

0.197

Gnomad4 SAS

AF:

0.0870

Gnomad4 FIN

AF:

0.0843

Gnomad4 NFE

AF:

0.0665

Gnomad4 OTH

AF:

0.0743

Alfa

AF:

0.0705

Hom.:

142

Bravo

AF:

0.0731

Asia WGS

AF:

0.150

AC:

520

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.47

DANN

Benign

0.71

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over