chr12-104313373-A-G

Variant names:

• chr12-104313373-A-G
• rs5018287
• NM_001093771.3:c.610+56A>G

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+56A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.535 in 1,354,846 control chromosomes in the GnomAD database, including 196,151 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 0.49 (18544 hom., cov: 32)
  • Exomes 𝑓: 0.54 (177607 hom.)
• Consequence: TXNRD1 NM_001093771.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.86
• Publications: 16 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.603 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001093771.3. 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.610+56A>G		intron	N/A	NP_001087240.1	Q16881-1
	TXNRD1	NM_003330.4		c.316+56A>G		intron	N/A	NP_003321.3
	TXNRD1	NM_001261445.2		c.310+56A>G		intron	N/A	NP_001248374.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TXNRD1	ENST00000525566.6	TSL:1 MANE Select	c.610+56A>G		intron	N/A	ENSP00000434516.1	Q16881-1
	TXNRD1	ENST00000526691.5	TSL:1	c.316+56A>G		intron	N/A	ENSP00000435929.1	Q16881-4
	TXNRD1	ENST00000503506.6	TSL:1	c.160+56A>G		intron	N/A	ENSP00000421934.2	Q16881-5

Frequencies

GnomAD3 genomes AF: 0.488 AC: 74105 AN: 151932 Hom.: 18534 Cov.: 32

Gnomad AFR AF: 0.381

Gnomad AMI AF: 0.538

Gnomad AMR AF: 0.506

Gnomad ASJ AF: 0.524

Gnomad EAS AF: 0.621

Gnomad SAS AF: 0.517

Gnomad FIN AF: 0.407

Gnomad MID AF: 0.468

Gnomad NFE AF: 0.545

Gnomad OTH AF: 0.520

GnomAD4 exome AF: 0.542 AC: 651366 AN: 1202796 Hom.: 177607 AF XY: 0.541 AC XY: 323520 AN XY: 598552

African (AFR) AF: 0.372 AC: 9765 AN: 26270

American (AMR) AF: 0.516 AC: 13315 AN: 25800

Ashkenazi Jewish (ASJ) AF: 0.552 AC: 12219 AN: 22142

East Asian (EAS) AF: 0.600 AC: 20398 AN: 34012

South Asian (SAS) AF: 0.505 AC: 34083 AN: 67486

European-Finnish (FIN) AF: 0.433 AC: 20807 AN: 48098

Middle Eastern (MID) AF: 0.493 AC: 2543 AN: 5162

European-Non Finnish (NFE) AF: 0.554 AC: 510995 AN: 922874

Other (OTH) AF: 0.535 AC: 27241 AN: 50952

GnomAD4 genome AF: 0.488 AC: 74148 AN: 152050 Hom.: 18544 Cov.: 32 AF XY: 0.481 AC XY: 35781 AN XY: 74316

African (AFR) AF: 0.381 AC: 15807 AN: 41468

American (AMR) AF: 0.506 AC: 7723 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.524 AC: 1815 AN: 3466

East Asian (EAS) AF: 0.621 AC: 3217 AN: 5182

South Asian (SAS) AF: 0.518 AC: 2498 AN: 4826

European-Finnish (FIN) AF: 0.407 AC: 4293 AN: 10556

Middle Eastern (MID) AF: 0.463 AC: 136 AN: 294

European-Non Finnish (NFE) AF: 0.545 AC: 37066 AN: 67966

Other (OTH) AF: 0.523 AC: 1102 AN: 2108

Alfa AF: 0.524 Hom.: 8887

Bravo AF: 0.493

Asia WGS AF: 0.542 AC: 1884 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.19
DANN	Benign	0.41
PhyloP100		-1.9
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: rs5018287; hg19: chr12-104707151;