rs3804047

chr22-19892114-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.949+3293T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.318 in 152,154 control chromosomes in the GnomAD database, including 7,748 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 0.32 (7748 hom., cov: 34)
• Consequence: TXNRD2 NM_006440.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0400

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.421 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TXNRD2	NM_006440.5	c.949+3293T>C		intron_variant		ENST00000400521.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TXNRD2	ENST00000400521.7	c.949+3293T>C		intron_variant		1	NM_006440.5	P4

Frequencies

GnomAD3 genomes AF: 0.318 AC: 48359 AN: 152036 Hom.: 7736 Cov.: 34

Gnomad AFR AF: 0.331

Gnomad AMI AF: 0.291

Gnomad AMR AF: 0.332

Gnomad ASJ AF: 0.378

Gnomad EAS AF: 0.436

Gnomad SAS AF: 0.349

Gnomad FIN AF: 0.348

Gnomad MID AF: 0.345

Gnomad NFE AF: 0.288

Gnomad OTH AF: 0.317

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.318 AC: 48403 AN: 152154 Hom.: 7748 Cov.: 34 AF XY: 0.324 AC XY: 24125 AN XY: 74368

Gnomad4 AFR AF: 0.331

Gnomad4 AMR AF: 0.333

Gnomad4 ASJ AF: 0.378

Gnomad4 EAS AF: 0.436

Gnomad4 SAS AF: 0.351

Gnomad4 FIN AF: 0.348

Gnomad4 NFE AF: 0.288

Gnomad4 OTH AF: 0.316

Alfa AF: 0.303 Hom.: 3704

Bravo AF: 0.316

Asia WGS AF: 0.406 AC: 1414 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	1.7
Dann	Benign	0.50
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

Other links and lift over

dbSNP: rs3804047; hg19: chr22-19879637;