rs200063300
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6BP7
The ENST00000400521.7(TXNRD2):c.1407C>T(p.Asn469=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000254 in 1,613,394 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000025 ( 0 hom. )
Consequence
TXNRD2
ENST00000400521.7 synonymous
ENST00000400521.7 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.312
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 Likely_benign. Variant got -4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.59).
BP6
Variant 22-19878128-G-A is Benign according to our data. Variant chr22-19878128-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 1127150.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Likely_benign=1}.
BP7
Synonymous conserved (PhyloP=-0.312 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TXNRD2 | NM_006440.5 | c.1407C>T | p.Asn469= | synonymous_variant | 16/18 | ENST00000400521.7 | NP_006431.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TXNRD2 | ENST00000400521.7 | c.1407C>T | p.Asn469= | synonymous_variant | 16/18 | 1 | NM_006440.5 | ENSP00000383365 | P4 |
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152238Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000201 AC: 5AN: 248968Hom.: 0 AF XY: 0.0000222 AC XY: 3AN XY: 135260
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GnomAD4 exome AF: 0.0000253 AC: 37AN: 1461156Hom.: 0 Cov.: 32 AF XY: 0.0000248 AC XY: 18AN XY: 726890
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GnomAD4 genome AF: 0.0000263 AC: 4AN: 152238Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74364
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:1
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 01, 2022 | The c.1407C>T variant (also known as p.N469N), located in coding exon 16 of the TXNRD2 gene, results from a C to T substitution at nucleotide position 1407. This nucleotide substitution does not change the asparagine at codon 469. This nucleotide position is poorly conserved in available vertebrate species. In silico splice site analysis for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Primary dilated cardiomyopathy Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 28, 2024 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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Details are displayed if max score is > 0.2
DS_DL_spliceai
Position offset: -38
Find out detailed SpliceAI scores and Pangolin per-transcript scores at