12-104313402-A-T

Variant names:

• chr12-104313402-A-T
• rs6539137
• NM_001093771.3:c.610+85A>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.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
• Publications: 8 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=-0.99).
• 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 rank	MANE	Protein	UniProt
TXNRD1	NM_001093771.3	c.610+85A>T		intron_variant	Intron 6 of 16	ENST00000525566.6	NP_001087240.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TXNRD1	ENST00000525566.6	c.610+85A>T		intron_variant	Intron 6 of 16	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

African (AFR) AF: 0.985 AC: 19714 AN: 20020

American (AMR) AF: 0.884 AC: 15756 AN: 17822

Ashkenazi Jewish (ASJ) AF: 0.940 AC: 17345 AN: 18460

East Asian (EAS) AF: 1.00 AC: 31391 AN: 31402

South Asian (SAS) AF: 0.941 AC: 52985 AN: 56286

European-Finnish (FIN) AF: 0.895 AC: 40126 AN: 44836

Middle Eastern (MID) AF: 0.951 AC: 4134 AN: 4348

European-Non Finnish (NFE) AF: 0.895 AC: 614019 AN: 686174

Other (OTH) AF: 0.913 AC: 37143 AN: 40666

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

African (AFR) AF: 0.981 AC: 40732 AN: 41528

American (AMR) AF: 0.894 AC: 13666 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.937 AC: 3252 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5184 AN: 5186

South Asian (SAS) AF: 0.941 AC: 4541 AN: 4828

European-Finnish (FIN) AF: 0.896 AC: 9496 AN: 10596

Middle Eastern (MID) AF: 0.973 AC: 286 AN: 294

European-Non Finnish (NFE) AF: 0.898 AC: 61098 AN: 68032

Other (OTH) AF: 0.932 AC: 1967 AN: 2110

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
PhyloP100		-3.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs6539137; hg19: chr12-104707180;