rs12158214

Positions:

• chr22-19884168-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006440.5(TXNRD2):​c.950-707G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.197 in 152,502 control chromosomes in the GnomAD database, including 3,656 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 0.20 (3648 hom., cov: 32)
  • Exomes 𝑓: 0.15 (8 hom.)
• Consequence: TXNRD2 NM_006440.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.125

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.334 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TXNRD2	NM_006440.5	c.950-707G>A		intron_variant		ENST00000400521.7	NP_006431.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TXNRD2	ENST00000400521.7	c.950-707G>A		intron_variant		1	NM_006440.5	ENSP00000383365	P4

Frequencies

GnomAD3 genomes AF: 0.197 AC: 29888 AN: 151876 Hom.: 3633 Cov.: 32

Gnomad AFR AF: 0.338

Gnomad AMI AF: 0.152

Gnomad AMR AF: 0.143

Gnomad ASJ AF: 0.199

Gnomad EAS AF: 0.00986

Gnomad SAS AF: 0.104

Gnomad FIN AF: 0.0914

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.161

Gnomad OTH AF: 0.181

GnomAD4 exome AF: 0.146 AC: 74 AN: 508 Hom.: 8 Cov.: 0 AF XY: 0.151 AC XY: 53 AN XY: 352

Gnomad4 AFR exome AF: 0.500

Gnomad4 AMR exome AF: 0.300

Gnomad4 ASJ exome AF: 0.167

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.125

Gnomad4 FIN exome AF: 0.0500

Gnomad4 NFE exome AF: 0.153

Gnomad4 OTH exome AF: 0.0938

GnomAD4 genome AF: 0.197 AC: 29946 AN: 151994 Hom.: 3648 Cov.: 32 AF XY: 0.191 AC XY: 14168 AN XY: 74312

Gnomad4 AFR AF: 0.338

Gnomad4 AMR AF: 0.143

Gnomad4 ASJ AF: 0.199

Gnomad4 EAS AF: 0.00988

Gnomad4 SAS AF: 0.104

Gnomad4 FIN AF: 0.0914

Gnomad4 NFE AF: 0.161

Gnomad4 OTH AF: 0.181

Alfa AF: 0.182 Hom.: 437

Bravo AF: 0.205

Asia WGS AF: 0.0810 AC: 281 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.5
DANN	Benign	0.63

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: rs12158214; hg19: chr22-19871691;