rs3788305

Positions:

• chr22-19884255-A-G

Variant summary

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

The NM_006440.5(TXNRD2):​c.950-794T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.537 in 152,274 control chromosomes in the GnomAD database, including 23,816 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 0.54 (23804 hom., cov: 33)
  • Exomes 𝑓: 0.43 (12 hom.)
• Consequence: TXNRD2 NM_006440.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.33

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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.773 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TXNRD2	NM_006440.5	c.950-794T>C		intron_variant		ENST00000400521.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TXNRD2	ENST00000400521.7	c.950-794T>C		intron_variant		1	NM_006440.5	P4

Frequencies

GnomAD3 genomes AF: 0.537 AC: 81636 AN: 152030 Hom.: 23740 Cov.: 33

Gnomad AFR AF: 0.780

Gnomad AMI AF: 0.461

Gnomad AMR AF: 0.456

Gnomad ASJ AF: 0.584

Gnomad EAS AF: 0.303

Gnomad SAS AF: 0.401

Gnomad FIN AF: 0.365

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.461

Gnomad OTH AF: 0.518

GnomAD4 exome AF: 0.429 AC: 54 AN: 126 Hom.: 12 Cov.: 0 AF XY: 0.442 AC XY: 46 AN XY: 104

Gnomad4 AFR exome AF: 0.500

Gnomad4 ASJ exome AF: 0.500

Gnomad4 SAS exome AF: 0.500

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 0.412

Gnomad4 OTH exome AF: 0.375

GnomAD4 genome AF: 0.537 AC: 81768 AN: 152148 Hom.: 23804 Cov.: 33 AF XY: 0.531 AC XY: 39479 AN XY: 74380

Gnomad4 AFR AF: 0.780

Gnomad4 AMR AF: 0.456

Gnomad4 ASJ AF: 0.584

Gnomad4 EAS AF: 0.303

Gnomad4 SAS AF: 0.403

Gnomad4 FIN AF: 0.365

Gnomad4 NFE AF: 0.461

Gnomad4 OTH AF: 0.517

Alfa AF: 0.487 Hom.: 19008

Bravo AF: 0.554

Asia WGS AF: 0.361 AC: 1255 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.13
DANN	Benign	0.39

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: rs3788305; hg19: chr22-19871778;