12-104337068-C-T

Variant names:

• chr12-104337068-C-T
• rs17202060
• NM_001093771.3:c.1747-2071C>T

Variant summary

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

The NM_001093771.3(TXNRD1):​c.1747-2071C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.298 in 151,770 control chromosomes in the GnomAD database, including 7,935 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 0.30 (7935 hom., cov: 32)
• Consequence: TXNRD1 NM_001093771.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.446
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.599 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TXNRD1	NM_001093771.3	c.1747-2071C>T		intron_variant	Intron 15 of 16	ENST00000525566.6	NP_001087240.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TXNRD1	ENST00000525566.6	c.1747-2071C>T		intron_variant	Intron 15 of 16	1	NM_001093771.3	ENSP00000434516.1

Frequencies

GnomAD3 genomes AF: 0.298 AC: 45210 AN: 151652 Hom.: 7926 Cov.: 32

Gnomad AFR AF: 0.172

Gnomad AMI AF: 0.389

Gnomad AMR AF: 0.362

Gnomad ASJ AF: 0.411

Gnomad EAS AF: 0.617

Gnomad SAS AF: 0.408

Gnomad FIN AF: 0.216

Gnomad MID AF: 0.306

Gnomad NFE AF: 0.333

Gnomad OTH AF: 0.331

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

GnomAD4 genome AF: 0.298 AC: 45232 AN: 151770 Hom.: 7935 Cov.: 32 AF XY: 0.298 AC XY: 22085 AN XY: 74194

African (AFR) AF: 0.172 AC: 7136 AN: 41456

American (AMR) AF: 0.363 AC: 5529 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.411 AC: 1419 AN: 3456

East Asian (EAS) AF: 0.617 AC: 3198 AN: 5186

South Asian (SAS) AF: 0.409 AC: 1967 AN: 4808

European-Finnish (FIN) AF: 0.216 AC: 2276 AN: 10556

Middle Eastern (MID) AF: 0.301 AC: 88 AN: 292

European-Non Finnish (NFE) AF: 0.333 AC: 22565 AN: 67774

Other (OTH) AF: 0.336 AC: 710 AN: 2110

Alfa AF: 0.326 Hom.: 11666

Bravo AF: 0.304

Asia WGS AF: 0.484 AC: 1682 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.93
DANN	Benign	0.82
PhyloP100		-0.45
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: rs17202060; hg19: chr12-104730846;