dbSNP rs35009941: TXNRD1:c.305-181C>G (chr12-104288750-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001093771.3(TXNRD1):c.305-181C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0136 in 1,478,786 control chromosomes in the GnomAD database, including 875 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 0.038 ( 297 hom., cov: 32)

Exomes 𝑓: 0.011 ( 578 hom. )

Consequence

TXNRD1
NM_001093771.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.299

Variant links:

Genes affected

TXNRD1 (HGNC:12437): (thioredoxin reductase 1) 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 an ubiquitously expressed, cytosolic form of TrxR, which 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. Alternative splicing, primarily at the 5' end, results in transcript variants encoding same or different isoforms, including a glutaredoxin-containing isoform that is predominantly expressed in testis. [provided by RefSeq, May 2017]

TXNRD1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.108 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TXNRD1	NM_001093771.3 link	c.305-181C>G		intron_variant	Intron 3 of 16	ENST00000525566.6	NP_001087240.1	Q16881-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TXNRD1	ENST00000525566.6 link	c.305-181C>G		intron_variant	Intron 3 of 16	1	NM_001093771.3	ENSP00000434516.1		Q16881-1

Frequencies

GnomAD3 genomes

AF:

0.0384

AC:

5841

AN:

152154

Hom.:

293

Cov.:

show subpopulations

Gnomad AFR

AF:

0.111

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0270

Gnomad ASJ

AF:

0.0245

Gnomad EAS

AF:

0.0196

Gnomad SAS

AF:

0.0770

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.00306

Gnomad OTH

AF:

0.0315

GnomAD3 exomes

AF:

0.0267

AC:

3284

AN:

122798

Hom.:

126

AF XY:

0.0282

AC XY:

1868

AN XY:

66140

show subpopulations

Gnomad AFR exome

AF:

0.120

Gnomad AMR exome

AF:

0.0140

Gnomad ASJ exome

AF:

0.0245

Gnomad EAS exome

AF:

0.0206

Gnomad SAS exome

AF:

0.0792

Gnomad FIN exome

AF:

0.000383

Gnomad NFE exome

AF:

0.00356

Gnomad OTH exome

AF:

0.0196

GnomAD4 exome

AF:

0.0108

AC:

14273

AN:

1326514

Hom.:

578

Cov.:

AF XY:

0.0124

AC XY:

8041

AN XY:

648990

show subpopulations

Gnomad4 AFR exome

AF:

0.117

Gnomad4 AMR exome

AF:

0.0150

Gnomad4 ASJ exome

AF:

0.0232

Gnomad4 EAS exome

AF:

0.0215

Gnomad4 SAS exome

AF:

0.0762

Gnomad4 FIN exome

AF:

0.000199

Gnomad4 NFE exome

AF:

0.00197

Gnomad4 OTH exome

AF:

0.0202

GnomAD4 genome

AF:

0.0385

AC:

5857

AN:

152272

Hom.:

297

Cov.:

AF XY:

0.0384

AC XY:

2858

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.111

Gnomad4 AMR

AF:

0.0269

Gnomad4 ASJ

AF:

0.0245

Gnomad4 EAS

AF:

0.0193

Gnomad4 SAS

AF:

0.0760

Gnomad4 FIN

AF:

0.000188

Gnomad4 NFE

AF:

0.00304

Gnomad4 OTH

AF:

0.0312

Alfa

AF:

0.0210

Hom.:

Bravo

AF:

0.0426

Asia WGS

AF:

0.0490

AC:

170

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

2.7

DANN

Benign

0.52

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

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