rs3788306

Positions:

• chr22-19884486-T-C

Variant summary

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

The ENST00000400521.7(TXNRD2):​c.950-1025A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.253 in 152,220 control chromosomes in the GnomAD database, including 5,153 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 0.25 (5140 hom., cov: 32)
  • Exomes 𝑓: 0.37 (13 hom.)
• Consequence: TXNRD2 ENST00000400521.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.591

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=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.293 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TXNRD2	NM_006440.5	c.950-1025A>G		intron_variant		ENST00000400521.7	NP_006431.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TXNRD2	ENST00000400521.7	c.950-1025A>G		intron_variant		1	NM_006440.5	ENSP00000383365	P4

Frequencies

GnomAD3 genomes AF: 0.253 AC: 38373 AN: 151924 Hom.: 5134 Cov.: 32

Gnomad AFR AF: 0.163

Gnomad AMI AF: 0.308

Gnomad AMR AF: 0.257

Gnomad ASJ AF: 0.372

Gnomad EAS AF: 0.277

Gnomad SAS AF: 0.218

Gnomad FIN AF: 0.274

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.296

Gnomad OTH AF: 0.264

GnomAD4 exome AF: 0.365 AC: 65 AN: 178 Hom.: 13 Cov.: 0 AF XY: 0.352 AC XY: 50 AN XY: 142

Gnomad4 AFR exome AF: 0.250

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.368

Gnomad4 OTH exome AF: 0.333

GnomAD4 genome AF: 0.252 AC: 38388 AN: 152042 Hom.: 5140 Cov.: 32 AF XY: 0.252 AC XY: 18699 AN XY: 74318

Gnomad4 AFR AF: 0.163

Gnomad4 AMR AF: 0.258

Gnomad4 ASJ AF: 0.372

Gnomad4 EAS AF: 0.277

Gnomad4 SAS AF: 0.219

Gnomad4 FIN AF: 0.274

Gnomad4 NFE AF: 0.296

Gnomad4 OTH AF: 0.263

Alfa AF: 0.296 Hom.: 11106

Bravo AF: 0.250

Asia WGS AF: 0.216 AC: 750 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	5.5
DANN	Benign	0.71

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs3788306; hg19: chr22-19872009;