ENST00000526691.5:c.-333C>G

Variant names:

• chr12-104287004-C-G
• rs11111979
• ENST00000526691.5:c.-333C>G

Variant summary

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

The ENST00000526691.5(TXNRD1):​c.-333C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.524 in 1,323,096 control chromosomes in the GnomAD database, including 184,757 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 0.47 (17428 hom., cov: 33)
  • Exomes 𝑓: 0.53 (167329 hom.)
• Consequence: TXNRD1 ENST00000526691.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.88
• Publications: 17 publications found

Genes affected

TXNRD1 (HGNC:12437): (thioredoxin reductase 1) 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 an ubiquitously expressed, cytosolic form of TrxR, which 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. Alternative splicing, primarily at the 5' end, results in transcript variants encoding same or different isoforms, including a glutaredoxin-containing isoform that is predominantly expressed in testis. [provided by RefSeq, May 2017]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.605 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000526691.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TXNRD1	NM_001093771.3	MANE Select	c.305-1927C>G		intron	N/A	NP_001087240.1
	TXNRD1	NM_003330.4		c.-333C>G		upstream_gene	N/A	NP_003321.3
	TXNRD1	NM_001261445.2		c.-424C>G		upstream_gene	N/A	NP_001248374.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TXNRD1	ENST00000526691.5	TSL:1	c.-333C>G		5_prime_UTR	Exon 1 of 15	ENSP00000435929.1
	TXNRD1	ENST00000503506.6	TSL:1	c.-252C>G		5_prime_UTR	Exon 1 of 15	ENSP00000421934.2
	TXNRD1	ENST00000525566.6	TSL:1 MANE Select	c.305-1927C>G		intron	N/A	ENSP00000434516.1

Frequencies

GnomAD3 genomes AF: 0.468 AC: 71180 AN: 151976 Hom.: 17426 Cov.: 33

Gnomad AFR AF: 0.325

Gnomad AMI AF: 0.551

Gnomad AMR AF: 0.496

Gnomad ASJ AF: 0.512

Gnomad EAS AF: 0.623

Gnomad SAS AF: 0.505

Gnomad FIN AF: 0.414

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.539

Gnomad OTH AF: 0.497

GnomAD4 exome AF: 0.532 AC: 622585 AN: 1171002 Hom.: 167329 Cov.: 59 AF XY: 0.530 AC XY: 298801 AN XY: 563252

African (AFR) AF: 0.312 AC: 8039 AN: 25790

American (AMR) AF: 0.504 AC: 7848 AN: 15564

Ashkenazi Jewish (ASJ) AF: 0.533 AC: 8390 AN: 15738

East Asian (EAS) AF: 0.610 AC: 15454 AN: 25324

South Asian (SAS) AF: 0.487 AC: 28439 AN: 58376

European-Finnish (FIN) AF: 0.441 AC: 7868 AN: 17832

Middle Eastern (MID) AF: 0.502 AC: 1580 AN: 3148

European-Non Finnish (NFE) AF: 0.541 AC: 520775 AN: 962566

Other (OTH) AF: 0.518 AC: 24192 AN: 46664

GnomAD4 genome AF: 0.468 AC: 71199 AN: 152094 Hom.: 17428 Cov.: 33 AF XY: 0.463 AC XY: 34412 AN XY: 74370

African (AFR) AF: 0.324 AC: 13458 AN: 41474

American (AMR) AF: 0.496 AC: 7580 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.512 AC: 1775 AN: 3468

East Asian (EAS) AF: 0.623 AC: 3219 AN: 5170

South Asian (SAS) AF: 0.505 AC: 2436 AN: 4826

European-Finnish (FIN) AF: 0.414 AC: 4373 AN: 10564

Middle Eastern (MID) AF: 0.452 AC: 133 AN: 294

European-Non Finnish (NFE) AF: 0.539 AC: 36666 AN: 67982

Other (OTH) AF: 0.501 AC: 1058 AN: 2112

Alfa AF: 0.498 Hom.: 2413

Bravo AF: 0.470

Asia WGS AF: 0.543 AC: 1886 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	16
DANN	Benign	0.71
PhyloP100		2.9
PromoterAI		-0.071	Neutral
Mutation Taster		=299/1	polymorphism (auto)

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: rs11111979; hg19: chr12-104680782;