12-104310058-A-G
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Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1
The NM_001093771.3(TXNRD1):c.415-1232A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.229 in 1,534,796 control chromosomes in the GnomAD database, including 41,970 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 0.23 ( 4111 hom., cov: 32)
Exomes 𝑓: 0.23 ( 37859 hom. )
Consequence
TXNRD1
NM_001093771.3 intron
NM_001093771.3 intron
Scores
14
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -1.76
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 (MetaRNN=0.0047516227).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.261 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TXNRD1 | NM_001093771.3 | c.415-1232A>G | intron_variant | ENST00000525566.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TXNRD1 | ENST00000525566.6 | c.415-1232A>G | intron_variant | 1 | NM_001093771.3 | P1 |
Frequencies
GnomAD3 genomes AF: 0.229 AC: 34812AN: 151874Hom.: 4105 Cov.: 32
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GnomAD3 exomes AF: 0.203 AC: 27268AN: 134078Hom.: 3209 AF XY: 0.212 AC XY: 15443AN XY: 72960
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GnomAD4 exome AF: 0.229 AC: 317222AN: 1382802Hom.: 37859 Cov.: 33 AF XY: 0.231 AC XY: 157234AN XY: 682116
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GnomAD4 genome AF: 0.229 AC: 34847AN: 151994Hom.: 4111 Cov.: 32 AF XY: 0.228 AC XY: 16957AN XY: 74272
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ClinVar
Not reported inComputational scores
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Name
Calibrated prediction
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Prediction
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T;.
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationTaster
Benign
P;P;P;P;P;P;P;P;P;P;P;P;P;P;P
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Benign
T;T
Sift4G
Benign
T;T
Vest4
0.025
ClinPred
T
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at