12-104313373-A-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001093771.3(TXNRD1):​c.610+56A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TXNRD1	NM_001093771.3	c.610+56A>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+56A>T		intron_variant	Intron 6 of 16	1	NM_001093771.3	ENSP00000434516.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1206228 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 600250

African (AFR) AF: 0.00 AC: 0 AN: 26324

American (AMR) AF: 0.00 AC: 0 AN: 25878

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22180

East Asian (EAS) AF: 0.00 AC: 0 AN: 34068

South Asian (SAS) AF: 0.00 AC: 0 AN: 67702

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48160

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5172

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 925650

Other (OTH) AF: 0.00 AC: 0 AN: 51094

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.14
DANN	Benign	0.54
PhyloP100		-1.9

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;