rs3788314

Positions:

• chr22-19901900-G-A

Variant summary

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

The NM_006440.5(TXNRD2):​c.663-2832C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.551 in 152,032 control chromosomes in the GnomAD database, including 24,194 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 0.55 (24194 hom., cov: 33)
• Consequence: TXNRD2 NM_006440.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.789

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 = 0.732 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TXNRD2	NM_006440.5	c.663-2832C>T		intron_variant		ENST00000400521.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TXNRD2	ENST00000400521.7	c.663-2832C>T		intron_variant		1	NM_006440.5	P4

Frequencies

GnomAD3 genomes AF: 0.551 AC: 83680 AN: 151914 Hom.: 24129 Cov.: 33

Gnomad AFR AF: 0.738

Gnomad AMI AF: 0.388

Gnomad AMR AF: 0.510

Gnomad ASJ AF: 0.599

Gnomad EAS AF: 0.437

Gnomad SAS AF: 0.549

Gnomad FIN AF: 0.496

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.464

Gnomad OTH AF: 0.538

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

GnomAD4 genome AF: 0.551 AC: 83806 AN: 152032 Hom.: 24194 Cov.: 33 AF XY: 0.551 AC XY: 40927 AN XY: 74336

Gnomad4 AFR AF: 0.739

Gnomad4 AMR AF: 0.510

Gnomad4 ASJ AF: 0.599

Gnomad4 EAS AF: 0.437

Gnomad4 SAS AF: 0.551

Gnomad4 FIN AF: 0.496

Gnomad4 NFE AF: 0.464

Gnomad4 OTH AF: 0.539

Alfa AF: 0.487 Hom.: 24482

Bravo AF: 0.560

Asia WGS AF: 0.536 AC: 1864 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	0.14
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: rs3788314; hg19: chr22-19889423;