rs113981920
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Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BS1BS2
The NM_025265.4(TSEN2):āc.1332A>Gā(p.Lys444=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000659 in 1,603,158 control chromosomes in the GnomAD database, including 7 homozygotes. 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: š 0.00068 ( 0 hom., cov: 32)
Exomes š: 0.00066 ( 7 hom. )
Consequence
TSEN2
NM_025265.4 synonymous
NM_025265.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 2.90
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 -14 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.53).
BP6
?
Variant 3-12531653-A-G is Benign according to our data. Variant chr3-12531653-A-G is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 160106.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=4, Uncertain_significance=2}.
BP7
?
Synonymous conserved (PhyloP=2.9 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.000657 (953/1450794) while in subpopulation MID AF= 0.00748 (43/5746). AF 95% confidence interval is 0.00571. There are 7 homozygotes in gnomad4_exome. There are 475 alleles in male gnomad4_exome subpopulation. Median coverage is 27. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAdExome4 at 7 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TSEN2 | NM_025265.4 | c.1332A>G | p.Lys444= | synonymous_variant | 11/12 | ENST00000284995.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TSEN2 | ENST00000284995.11 | c.1332A>G | p.Lys444= | synonymous_variant | 11/12 | 1 | NM_025265.4 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.000677 AC: 103AN: 152246Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000983 AC: 247AN: 251230Hom.: 1 AF XY: 0.000869 AC XY: 118AN XY: 135792
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GnomAD4 exome AF: 0.000657 AC: 953AN: 1450794Hom.: 7 Cov.: 27 AF XY: 0.000657 AC XY: 475AN XY: 722538
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GnomAD4 genome ? AF: 0.000676 AC: 103AN: 152364Hom.: 0 Cov.: 32 AF XY: 0.000658 AC XY: 49AN XY: 74512
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:2Benign:4
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not provided Uncertain:1Benign:3
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Feb 05, 2021 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 15, 2024 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Dec 23, 2015 | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | May 01, 2024 | TSEN2: BP4, BP7 - |
Pontoneocerebellar hypoplasia Uncertain:1
Uncertain significance, 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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Mar 16, 2017 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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