rs17745445

chr22-19920271-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.173-672C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.132 in 152,182 control chromosomes in the GnomAD database, including 1,442 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 0.13 (1442 hom., cov: 32)
• Consequence: TXNRD2 NM_006440.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.800

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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.145 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TXNRD2	NM_006440.5	c.173-672C>T		intron_variant		ENST00000400521.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TXNRD2	ENST00000400521.7	c.173-672C>T		intron_variant		1	NM_006440.5	P4

Frequencies

GnomAD3 genomes AF: 0.132 AC: 20056 AN: 152064 Hom.: 1435 Cov.: 32

Gnomad AFR AF: 0.135

Gnomad AMI AF: 0.0725

Gnomad AMR AF: 0.113

Gnomad ASJ AF: 0.151

Gnomad EAS AF: 0.0104

Gnomad SAS AF: 0.105

Gnomad FIN AF: 0.120

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.148

Gnomad OTH AF: 0.128

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

GnomAD4 genome AF: 0.132 AC: 20084 AN: 152182 Hom.: 1442 Cov.: 32 AF XY: 0.128 AC XY: 9557 AN XY: 74398

Gnomad4 AFR AF: 0.135

Gnomad4 AMR AF: 0.113

Gnomad4 ASJ AF: 0.151

Gnomad4 EAS AF: 0.0104

Gnomad4 SAS AF: 0.106

Gnomad4 FIN AF: 0.120

Gnomad4 NFE AF: 0.148

Gnomad4 OTH AF: 0.129

Alfa AF: 0.140 Hom.: 197

Bravo AF: 0.131

Asia WGS AF: 0.0760 AC: 264 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	5.5
Dann	Benign	0.66

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: rs17745445; hg19: chr22-19907794;