rs1128446
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Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1
The ENST00000526691.5(TXNRD1):c.-273C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.226 in 1,415,598 control chromosomes in the GnomAD database, including 37,570 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 0.22 ( 3725 hom., cov: 33)
Exomes 𝑓: 0.23 ( 33845 hom. )
Consequence
TXNRD1
ENST00000526691.5 5_prime_UTR
ENST00000526691.5 5_prime_UTR
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -1.50
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -12 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.8).
BA1
?
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.235 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TXNRD1 | NM_001093771.3 | c.305-1867C>G | intron_variant | ENST00000525566.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TXNRD1 | ENST00000525566.6 | c.305-1867C>G | intron_variant | 1 | NM_001093771.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.219 AC: 33227AN: 152044Hom.: 3721 Cov.: 33
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GnomAD4 exome AF: 0.227 AC: 287127AN: 1263436Hom.: 33845 Cov.: 33 AF XY: 0.228 AC XY: 139607AN XY: 612410
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GnomAD4 genome ? AF: 0.219 AC: 33255AN: 152162Hom.: 3725 Cov.: 33 AF XY: 0.218 AC XY: 16205AN XY: 74404
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ClinVar
Not reported inComputational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at