chr22-36476826-C-T
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Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2
The NM_012473.4(TXN2):c.294G>A(p.Pro98=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00742 in 1,614,164 control chromosomes in the GnomAD database, including 68 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0059 ( 7 hom., cov: 32)
Exomes 𝑓: 0.0076 ( 61 hom. )
Consequence
TXN2
NM_012473.4 synonymous
NM_012473.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.65
Genes affected
TXN2 (HGNC:17772): (thioredoxin 2) This nuclear gene encodes a mitochondrial member of the thioredoxin family, a group of small multifunctional redox-active proteins. The encoded protein may play important roles in the regulation of the mitochondrial membrane potential and in protection against oxidant-induced apoptosis. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -17 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.68).
BP6
Variant 22-36476826-C-T is Benign according to our data. Variant chr22-36476826-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 774540.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-1.65 with no splicing effect.
BS2
High Homozygotes in GnomAd4 at 7 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TXN2 | NM_012473.4 | c.294G>A | p.Pro98= | synonymous_variant | 3/4 | ENST00000216185.7 | |
TXN2 | XM_006724226.2 | c.294G>A | p.Pro98= | synonymous_variant | 3/4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TXN2 | ENST00000216185.7 | c.294G>A | p.Pro98= | synonymous_variant | 3/4 | 1 | NM_012473.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00586 AC: 892AN: 152158Hom.: 7 Cov.: 32
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GnomAD3 exomes AF: 0.00635 AC: 1597AN: 251486Hom.: 9 AF XY: 0.00645 AC XY: 877AN XY: 135916
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GnomAD4 exome AF: 0.00758 AC: 11088AN: 1461888Hom.: 61 Cov.: 33 AF XY: 0.00754 AC XY: 5486AN XY: 727244
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GnomAD4 genome AF: 0.00585 AC: 891AN: 152276Hom.: 7 Cov.: 32 AF XY: 0.00561 AC XY: 418AN XY: 74466
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:3
Benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jul 01, 2024 | TXN2: BP4, BP7, BS1, BS2 - |
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 29, 2024 | - - |
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Combined oxidative phosphorylation deficiency 29 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Oct 05, 2021 | - - |
TXN2-related disorder Benign:1
Benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Jan 13, 2020 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
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
Find out detailed SpliceAI scores and Pangolin per-transcript scores at