dbSNP rs5992493: TXNRD2:c.*1100T>C (chr22-19894033-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001282512.3(TXNRD2):c.*1100T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.267 in 152,196 control chromosomes in the GnomAD database, including 7,699 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 0.27 ( 7699 hom., cov: 33)

Exomes 𝑓: 0.25 ( 0 hom. )

Consequence

TXNRD2
NM_001282512.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.314

Variant links:

Genes affected

TXNRD2 (HGNC:18155): (thioredoxin reductase 2) 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 a mitochondrial form important for scavenging reactive oxygen species in mitochondria. 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 encoding different isoforms, including a few localized in the cytosol and some lacking the C-terminal Sec residue, have been found for this gene. [provided by RefSeq, Jun 2017]

TXNRD2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.0).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.529 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TXNRD2	NM_006440.5 link	c.949+1374T>C		intron_variant	Intron 11 of 17	ENST00000400521.7	NP_006431.2	Q9NNW7-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TXNRD2	ENST00000400521.7 link	c.949+1374T>C		intron_variant	Intron 11 of 17	1	NM_006440.5	ENSP00000383365.1		Q9NNW7-1

Frequencies

GnomAD3 genomes

AF:

0.267

AC:

40559

AN:

152062

Hom.:

7664

Cov.:

show subpopulations

Gnomad AFR

AF:

0.534

Gnomad AMI

AF:

0.0746

Gnomad AMR

AF:

0.200

Gnomad ASJ

AF:

0.177

Gnomad EAS

AF:

0.0558

Gnomad SAS

AF:

0.206

Gnomad FIN

AF:

0.125

Gnomad MID

AF:

0.149

Gnomad NFE

AF:

0.170

Gnomad OTH

AF:

0.243

GnomAD4 exome

AF:

0.250

AC:

AN:

Hom.:

Cov.:

AF XY:

0.200

AC XY:

AN XY:

show subpopulations

Gnomad4 AFR exome

AC:

AN:

Gnomad4 AMR exome

AC:

AN:

Gnomad4 ASJ exome

AC:

AN:

Gnomad4 EAS exome

AC:

AN:

Gnomad4 SAS exome

AC:

AN:

Gnomad4 FIN exome

AF:

0.167

AC:

AN:

Gnomad4 NFE exome

AF:

0.333

AC:

AN:

Gnomad4 Remaining exome

AF:

0.250

AC:

AN:

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.267

AC:

40666

AN:

152180

Hom.:

7699

Cov.:

AF XY:

0.261

AC XY:

19419

AN XY:

74404

show subpopulations

Gnomad4 AFR

AF:

0.535

AC:

0.534889

AN:

0.534889

Gnomad4 AMR

AF:

0.200

AC:

0.199765

AN:

0.199765

Gnomad4 ASJ

AF:

0.177

AC:

0.177419

AN:

0.177419

Gnomad4 EAS

AF:

0.0559

AC:

0.0559414

AN:

0.0559414

Gnomad4 SAS

AF:

0.207

AC:

0.206625

AN:

0.206625

Gnomad4 FIN

AF:

0.125

AC:

0.125495

AN:

0.125495

Gnomad4 NFE

AF:

0.170

AC:

0.170118

AN:

0.170118

Gnomad4 OTH

AF:

0.244

AC:

0.244076

AN:

0.244076

Heterozygous variant carriers

1337

2675

4012

5350

6687

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

378

756

1134

1512

1890

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.209

Hom.:

2510

Bravo

AF:

0.284

Asia WGS

AF:

0.161

AC:

558

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

3.6

DANN

Benign

0.53

Mutation Taster

=100/0

polymorphism (auto)

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