chr12-104287064-C-G

Variant names:

• chr12-104287064-C-G
• rs1128446
• ENST00000526207.1:n.33C>G

Variant summary

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

The ENST00000526207.1(TXNRD1):​n.33C>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.226 in 1,415,598 control chromosomes in the GnomAD database, including 37,570 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 0.22 (3725 hom., cov: 33)
  • Exomes 𝑓: 0.23 (33845 hom.)
• Consequence: TXNRD1 ENST00000526207.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.50
• Publications: 11 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=-0.8).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.235 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TXNRD1	NM_001093771.3	c.305-1867C>G		intron_variant	Intron 3 of 16	ENST00000525566.6	NP_001087240.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TXNRD1	ENST00000525566.6	c.305-1867C>G		intron_variant	Intron 3 of 16	1	NM_001093771.3	ENSP00000434516.1

Frequencies

GnomAD3 genomes AF: 0.219 AC: 33227 AN: 152044 Hom.: 3721 Cov.: 33

Gnomad AFR AF: 0.234

Gnomad AMI AF: 0.268

Gnomad AMR AF: 0.175

Gnomad ASJ AF: 0.275

Gnomad EAS AF: 0.0196

Gnomad SAS AF: 0.246

Gnomad FIN AF: 0.207

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.230

Gnomad OTH AF: 0.223

GnomAD4 exome AF: 0.227 AC: 287127 AN: 1263436 Hom.: 33845 Cov.: 33 AF XY: 0.228 AC XY: 139607 AN XY: 612410

African (AFR) AF: 0.243 AC: 6740 AN: 27788

American (AMR) AF: 0.157 AC: 2980 AN: 18996

Ashkenazi Jewish (ASJ) AF: 0.259 AC: 4739 AN: 18326

East Asian (EAS) AF: 0.0147 AC: 491 AN: 33304

South Asian (SAS) AF: 0.256 AC: 15922 AN: 62124

European-Finnish (FIN) AF: 0.191 AC: 5225 AN: 27366

Middle Eastern (MID) AF: 0.266 AC: 932 AN: 3508

European-Non Finnish (NFE) AF: 0.234 AC: 238440 AN: 1019788

Other (OTH) AF: 0.223 AC: 11658 AN: 52236

GnomAD4 genome AF: 0.219 AC: 33255 AN: 152162 Hom.: 3725 Cov.: 33 AF XY: 0.218 AC XY: 16205 AN XY: 74404

African (AFR) AF: 0.234 AC: 9717 AN: 41484

American (AMR) AF: 0.175 AC: 2674 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.275 AC: 952 AN: 3468

East Asian (EAS) AF: 0.0195 AC: 101 AN: 5184

South Asian (SAS) AF: 0.246 AC: 1189 AN: 4824

European-Finnish (FIN) AF: 0.207 AC: 2197 AN: 10600

Middle Eastern (MID) AF: 0.289 AC: 85 AN: 294

European-Non Finnish (NFE) AF: 0.230 AC: 15628 AN: 68002

Other (OTH) AF: 0.222 AC: 468 AN: 2106

Alfa AF: 0.129 Hom.: 234

Bravo AF: 0.213

Asia WGS AF: 0.153 AC: 534 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	1.7
DANN	Benign	0.58
PhyloP100		-1.5
PromoterAI		0.084	Neutral
Mutation Taster		=100/0	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: rs1128446; hg19: chr12-104680842;