chr3-126654076-G-A

Variant names:

• chr3-126654076-G-A
• rs11718498
• NM_052883.3:c.243+672C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_052883.3(TXNRD3):​c.243+672C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.368 in 151,362 control chromosomes in the GnomAD database, including 11,093 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 0.37 (11093 hom., cov: 31)
• Consequence: TXNRD3 NM_052883.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.459
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.602 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TXNRD3	NM_052883.3	c.243+672C>T		intron_variant	Intron 1 of 15	ENST00000524230.9	NP_443115.1
TXNRD3	NM_001173513.3	c.243+672C>T		intron_variant	Intron 1 of 14		NP_001166984.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TXNRD3	ENST00000524230.9	c.243+672C>T		intron_variant	Intron 1 of 15	1	NM_052883.3	ENSP00000430031.4
TXNRD3	ENST00000523403.3	c.243+672C>T		intron_variant	Intron 1 of 14	2		ENSP00000429584.3

Frequencies

GnomAD3 genomes AF: 0.368 AC: 55639 AN: 151274 Hom.: 11104 Cov.: 31

Gnomad AFR AF: 0.204

Gnomad AMI AF: 0.421

Gnomad AMR AF: 0.367

Gnomad ASJ AF: 0.439

Gnomad EAS AF: 0.620

Gnomad SAS AF: 0.395

Gnomad FIN AF: 0.448

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.429

Gnomad OTH AF: 0.374

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

GnomAD4 genome AF: 0.368 AC: 55644 AN: 151362 Hom.: 11093 Cov.: 31 AF XY: 0.371 AC XY: 27430 AN XY: 73870

African (AFR) AF: 0.204 AC: 8411 AN: 41208

American (AMR) AF: 0.366 AC: 5570 AN: 15222

Ashkenazi Jewish (ASJ) AF: 0.439 AC: 1522 AN: 3468

East Asian (EAS) AF: 0.620 AC: 3201 AN: 5164

South Asian (SAS) AF: 0.395 AC: 1891 AN: 4788

European-Finnish (FIN) AF: 0.448 AC: 4613 AN: 10308

Middle Eastern (MID) AF: 0.432 AC: 126 AN: 292

European-Non Finnish (NFE) AF: 0.429 AC: 29147 AN: 67904

Other (OTH) AF: 0.372 AC: 781 AN: 2100

Alfa AF: 0.408 Hom.: 38939

Bravo AF: 0.357

Asia WGS AF: 0.450 AC: 1561 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.5
DANN	Benign	0.64
PhyloP100		0.46

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

Other links and lift over

dbSNP: rs11718498; hg19: chr3-126372919;