rs78685815
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_025265.4(TSEN2):c.162G>A(p.Ala54Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0261 in 1,613,972 control chromosomes in the GnomAD database, including 1,739 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.065 ( 702 hom., cov: 32)
Exomes 𝑓: 0.022 ( 1037 hom. )
Consequence
TSEN2
NM_025265.4 synonymous
NM_025265.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -3.64
Genes affected
TSEN2 (HGNC:28422): (tRNA splicing endonuclease subunit 2) This gene encodes one of the subunits of the tRNA splicing endonuclease. This endonuclease catalyzes the first step in RNA splicing which is the removal of introns. Mutations in this gene have been associated with pontocerebellar hypoplasia type 2. A pseudogene has been identified on chromosome 4. Multiple transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Feb 2009]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.72).
BP6
Variant 3-12489962-G-A is Benign according to our data. Variant chr3-12489962-G-A is described in ClinVar as [Benign]. Clinvar id is 137753.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-3.64 with no splicing effect.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.166 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TSEN2 | NM_025265.4 | c.162G>A | p.Ala54Ala | synonymous_variant | 2/12 | ENST00000284995.11 | NP_079541.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TSEN2 | ENST00000284995.11 | c.162G>A | p.Ala54Ala | synonymous_variant | 2/12 | 1 | NM_025265.4 | ENSP00000284995.6 |
Frequencies
GnomAD3 genomes AF: 0.0647 AC: 9842AN: 152120Hom.: 698 Cov.: 32
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GnomAD3 exomes AF: 0.0354 AC: 8910AN: 251370Hom.: 390 AF XY: 0.0329 AC XY: 4475AN XY: 135868
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GnomAD4 exome AF: 0.0221 AC: 32341AN: 1461734Hom.: 1037 Cov.: 32 AF XY: 0.0221 AC XY: 16090AN XY: 727164
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GnomAD4 genome AF: 0.0648 AC: 9859AN: 152238Hom.: 702 Cov.: 32 AF XY: 0.0646 AC XY: 4806AN XY: 74434
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ClinVar
Significance: Benign
Submissions summary: Benign:6
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:3
Benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Feb 08, 2013 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 04, 2014 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
not provided Benign:2
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Feb 01, 2024 | - - |
Pontoneocerebellar hypoplasia Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Computational scores
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BayesDel_noAF
Benign
CADD
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DANN
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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