12-104313402-A-T

Position:

• chr12-104313402-A-T

Variant summary

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

The NM_001093771.3(TXNRD1):​c.610+85A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.908 in 1,072,262 control chromosomes in the GnomAD database, including 442,679 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 0.93 (65485 hom., cov: 31)
  • Exomes 𝑓: 0.91 (377194 hom.)
• Consequence: TXNRD1 NM_001093771.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.55

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TXNRD1	NM_001093771.3	c.610+85A>T		intron_variant		ENST00000525566.6	NP_001087240.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TXNRD1	ENST00000525566.6	c.610+85A>T		intron_variant		1	NM_001093771.3	ENSP00000434516.1

Frequencies

GnomAD3 genomes AF: 0.926 AC: 140928 AN: 152130 Hom.: 65432 Cov.: 31

Gnomad AFR AF: 0.981

Gnomad AMI AF: 0.899

Gnomad AMR AF: 0.894

Gnomad ASJ AF: 0.937

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.941

Gnomad FIN AF: 0.896

Gnomad MID AF: 0.972

Gnomad NFE AF: 0.898

Gnomad OTH AF: 0.932

GnomAD4 exome AF: 0.905 AC: 832613 AN: 920014 Hom.: 377194 AF XY: 0.906 AC XY: 419602 AN XY: 462972

Gnomad4 AFR exome AF: 0.985

Gnomad4 AMR exome AF: 0.884

Gnomad4 ASJ exome AF: 0.940

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 0.941

Gnomad4 FIN exome AF: 0.895

Gnomad4 NFE exome AF: 0.895

Gnomad4 OTH exome AF: 0.913

GnomAD4 genome AF: 0.926 AC: 141040 AN: 152248 Hom.: 65485 Cov.: 31 AF XY: 0.926 AC XY: 68955 AN XY: 74428

Gnomad4 AFR AF: 0.981

Gnomad4 AMR AF: 0.894

Gnomad4 ASJ AF: 0.937

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 0.941

Gnomad4 FIN AF: 0.896

Gnomad4 NFE AF: 0.898

Gnomad4 OTH AF: 0.932

Alfa AF: 0.914 Hom.: 7733

Bravo AF: 0.927

Asia WGS AF: 0.973 AC: 3385 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.17
DANN	Benign	0.25
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs6539137; hg19: chr12-104707180;