rs9637365

chr3-126651323-T-C

Variant summary

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

The NM_052883.3(TXNRD3):c.243+3425A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.483 in 152,034 control chromosomes in the GnomAD database, including 19,186 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 0.48 (19186 hom., cov: 32)
• Consequence: TXNRD3 NM_052883.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.209

Genes affected

TXNRD3 (HGNC:20667): (thioredoxin reductase 3) 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 the third TrxR, which unlike the other two isozymes, contains an additional N-terminal glutaredoxin (Grx) domain, and shows highest expression in testis. The Grx domain allows this isozyme to participate in both Trx and glutathione systems. 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 have been found for this gene. Experimental evidence suggests the use of a non-AUG (CUG) codon as a translation initiation codon (PMID:20018845). [provided by RefSeq, Aug 2017]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.624 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TXNRD3	NM_052883.3	c.243+3425A>G		intron_variant		ENST00000524230.9
TXNRD3	NM_001173513.3	c.243+3425A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TXNRD3	ENST00000524230.9	c.243+3425A>G		intron_variant		1	NM_052883.3	P1
TXNRD3	ENST00000523403.3	c.243+3425A>G		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.484 AC: 73505 AN: 151916 Hom.: 19196 Cov.: 32

Gnomad AFR AF: 0.272

Gnomad AMI AF: 0.611

Gnomad AMR AF: 0.461

Gnomad ASJ AF: 0.559

Gnomad EAS AF: 0.642

Gnomad SAS AF: 0.498

Gnomad FIN AF: 0.600

Gnomad MID AF: 0.528

Gnomad NFE AF: 0.581

Gnomad OTH AF: 0.492

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

GnomAD4 genome AF: 0.483 AC: 73506 AN: 152034 Hom.: 19186 Cov.: 32 AF XY: 0.486 AC XY: 36080 AN XY: 74306

Gnomad4 AFR AF: 0.272

Gnomad4 AMR AF: 0.460

Gnomad4 ASJ AF: 0.559

Gnomad4 EAS AF: 0.643

Gnomad4 SAS AF: 0.498

Gnomad4 FIN AF: 0.600

Gnomad4 NFE AF: 0.581

Gnomad4 OTH AF: 0.487

Alfa AF: 0.568 Hom.: 49424

Bravo AF: 0.468

Asia WGS AF: 0.505 AC: 1756 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
Cadd	Benign	10
Dann	Benign	0.91

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: rs9637365; hg19: chr3-126370166;