chr22-19875633-T-TG
Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBS1BS2
The NM_006440.5(TXNRD2):c.*239_*240insC variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0112 in 151,090 control chromosomes in the GnomAD database, including 20 homozygotes. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.011 ( 20 hom., cov: 23)
Exomes 𝑓: 0.012 ( 0 hom. )
Consequence
TXNRD2
NM_006440.5 3_prime_UTR
NM_006440.5 3_prime_UTR
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.00
Genes affected
TXNRD2 (HGNC:18155): (thioredoxin reductase 2) 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 a mitochondrial form important for scavenging reactive oxygen species in mitochondria. It 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. Alternatively spliced transcript variants encoding different isoforms, including a few localized in the cytosol and some lacking the C-terminal Sec residue, have been found for this gene. [provided by RefSeq, Jun 2017]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -10 ACMG points.
BP6
?
Variant 22-19875633-T-TG is Benign according to our data. Variant chr22-19875633-T-TG is described in ClinVar as [Likely_benign]. Clinvar id is 1320491.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
?
Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.0112 (1694/150926) while in subpopulation AMR AF= 0.0388 (588/15174). AF 95% confidence interval is 0.0362. There are 20 homozygotes in gnomad4. There are 898 alleles in male gnomad4 subpopulation. Median coverage is 23. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd at 20 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TXNRD2 | NM_006440.5 | c.*239_*240insC | 3_prime_UTR_variant | 18/18 | ENST00000400521.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TXNRD2 | ENST00000400521.7 | c.*239_*240insC | 3_prime_UTR_variant | 18/18 | 1 | NM_006440.5 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.0112 AC: 1692AN: 150808Hom.: 20 Cov.: 23
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GnomAD4 exome AF: 0.0122 AC: 2AN: 164Hom.: 0 Cov.: 0 AF XY: 0.00781 AC XY: 1AN XY: 128
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GnomAD4 genome ? AF: 0.0112 AC: 1694AN: 150926Hom.: 20 Cov.: 23 AF XY: 0.0122 AC XY: 898AN XY: 73678
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 19, 2021 | - - |
Computational scores
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at