rs5992493

Positions:

• chr22-19894033-A-G

Variant summary

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

The ENST00000491939.6(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 ENST00000491939.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.314

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=-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/exons	MANE	Protein	UniProt
TXNRD2	NM_006440.5	c.949+1374T>C		intron_variant		ENST00000400521.7	NP_006431.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TXNRD2	ENST00000400521.7	c.949+1374T>C		intron_variant		1	NM_006440.5	ENSP00000383365	P4

Frequencies

GnomAD3 genomes AF: 0.267 AC: 40559 AN: 152062 Hom.: 7664 Cov.: 33

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: 4 AN: 16 Hom.: 0 Cov.: 0 AF XY: 0.200 AC XY: 2 AN XY: 10

Gnomad4 FIN exome AF: 0.167

Gnomad4 NFE exome AF: 0.333

Gnomad4 OTH exome AF: 0.250

GnomAD4 genome AF: 0.267 AC: 40666 AN: 152180 Hom.: 7699 Cov.: 33 AF XY: 0.261 AC XY: 19419 AN XY: 74404

Gnomad4 AFR AF: 0.535

Gnomad4 AMR AF: 0.200

Gnomad4 ASJ AF: 0.177

Gnomad4 EAS AF: 0.0559

Gnomad4 SAS AF: 0.207

Gnomad4 FIN AF: 0.125

Gnomad4 NFE AF: 0.170

Gnomad4 OTH AF: 0.244

Alfa AF: 0.208 Hom.: 2255

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

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: rs5992493; hg19: chr22-19881556;