rs5993853

chr22-19892415-T-Cchr22-19892415-T-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+2992A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.781 in 152,288 control chromosomes in the GnomAD database, including 47,400 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 0.78 (47400 hom., cov: 35)
• Consequence: TXNRD2 NM_006440.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.38

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 (AFR) allele frequency at 95% confidence interval = 0.932 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TXNRD2	NM_006440.5	c.949+2992A>G		intron_variant		ENST00000400521.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TXNRD2	ENST00000400521.7	c.949+2992A>G		intron_variant		1	NM_006440.5	P4

Frequencies

GnomAD3 genomes AF: 0.780 AC: 118734 AN: 152170 Hom.: 47332 Cov.: 35

Gnomad AFR AF: 0.940

Gnomad AMI AF: 0.698

Gnomad AMR AF: 0.802

Gnomad ASJ AF: 0.702

Gnomad EAS AF: 0.929

Gnomad SAS AF: 0.829

Gnomad FIN AF: 0.702

Gnomad MID AF: 0.618

Gnomad NFE AF: 0.683

Gnomad OTH AF: 0.747

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

GnomAD4 genome AF: 0.781 AC: 118866 AN: 152288 Hom.: 47400 Cov.: 35 AF XY: 0.783 AC XY: 58314 AN XY: 74460

Gnomad4 AFR AF: 0.940

Gnomad4 AMR AF: 0.802

Gnomad4 ASJ AF: 0.702

Gnomad4 EAS AF: 0.929

Gnomad4 SAS AF: 0.830

Gnomad4 FIN AF: 0.702

Gnomad4 NFE AF: 0.682

Gnomad4 OTH AF: 0.748

Alfa AF: 0.695 Hom.: 27934

Bravo AF: 0.795

Asia WGS AF: 0.866 AC: 3010 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	5.6
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: rs5993853; hg19: chr22-19879938; COSMIC: COSV57635866; COSMIC: COSV57635866;