22-19875633-TG-T

Position:

• chr22-19875633-TG-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_006440.5(TXNRD2):​c.*239del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.288 in 151,008 control chromosomes in the GnomAD database, including 9,860 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.29 (9856 hom., cov: 23)
  • Exomes 𝑓: 0.20 (4 hom.)
• Consequence: TXNRD2 NM_006440.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.00

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 -10 ACMG points.

• BP6: Variant 22-19875633-TG-T is Benign according to our data. Variant chr22-19875633-TG-T is described in ClinVar as [Benign]. Clinvar id is 1239595.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.626 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TXNRD2	NM_006440.5	c.*239del		3_prime_UTR_variant	18/18	ENST00000400521.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TXNRD2	ENST00000400521.7	c.*239del		3_prime_UTR_variant	18/18	1	NM_006440.5	P4

Frequencies

GnomAD3 genomes AF: 0.288 AC: 43390 AN: 150730 Hom.: 9810 Cov.: 23

Gnomad AFR AF: 0.631

Gnomad AMI AF: 0.153

Gnomad AMR AF: 0.201

Gnomad ASJ AF: 0.217

Gnomad EAS AF: 0.0329

Gnomad SAS AF: 0.185

Gnomad FIN AF: 0.0959

Gnomad MID AF: 0.239

Gnomad NFE AF: 0.160

Gnomad OTH AF: 0.253

GnomAD4 exome AF: 0.200 AC: 32 AN: 160 Hom.: 4 Cov.: 0 AF XY: 0.211 AC XY: 27 AN XY: 128

Gnomad4 AFR exome AF: 0.600

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 1.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.177

Gnomad4 OTH exome AF: 0.167

GnomAD4 genome AF: 0.288 AC: 43505 AN: 150848 Hom.: 9856 Cov.: 23 AF XY: 0.283 AC XY: 20839 AN XY: 73642

Gnomad4 AFR AF: 0.632

Gnomad4 AMR AF: 0.201

Gnomad4 ASJ AF: 0.217

Gnomad4 EAS AF: 0.0329

Gnomad4 SAS AF: 0.186

Gnomad4 FIN AF: 0.0959

Gnomad4 NFE AF: 0.160

Gnomad4 OTH AF: 0.253

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 23, 2018

- -

Computational scores

Source: dbNSFP v4.3

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: rs59339361; hg19: chr22-19863156;