rs184898622
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Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2
The NM_001077446.4(TSEN34):c.39G>A(p.Val13=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000799 in 1,549,440 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0039 ( 3 hom., cov: 32)
Exomes 𝑓: 0.00047 ( 1 hom. )
Consequence
TSEN34
NM_001077446.4 synonymous
NM_001077446.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.05
Genes affected
TSEN34 (HGNC:15506): (tRNA splicing endonuclease subunit 34) This gene encodes a catalytic subunit of the tRNA splicing endonuclease, which catalyzes the removal of introns from precursor tRNAs. The endonuclease complex is also associated with a pre-mRNA 3-prime end processing factor. A mutation in this gene results in the neurological disorder pontocerebellar hypoplasia type 2. Multiple alternatively spliced variants, encoding the same protein, have been identified.[provided by RefSeq, Oct 2009]
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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=-0.5).
BP6
?
Variant 19-54191403-G-A is Benign according to our data. Variant chr19-54191403-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 160120.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-54191403-G-A is described in Lovd as [Likely_benign].
BP7
?
Synonymous conserved (PhyloP=1.05 with no splicing effect.
BS2
?
High Homozygotes in GnomAd4 at 3 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TSEN34 | NM_001077446.4 | c.39G>A | p.Val13= | synonymous_variant | 1/4 | ENST00000396388.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TSEN34 | ENST00000396388.3 | c.39G>A | p.Val13= | synonymous_variant | 1/4 | 1 | NM_001077446.4 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.00387 AC: 589AN: 152198Hom.: 3 Cov.: 32
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GnomAD3 exomes AF: 0.00100 AC: 147AN: 146602Hom.: 1 AF XY: 0.000812 AC XY: 64AN XY: 78842
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GnomAD4 exome AF: 0.000465 AC: 650AN: 1397130Hom.: 1 Cov.: 35 AF XY: 0.000422 AC XY: 291AN XY: 689292
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GnomAD4 genome ? AF: 0.00386 AC: 588AN: 152310Hom.: 3 Cov.: 32 AF XY: 0.00385 AC XY: 287AN XY: 74468
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | Oct 11, 2019 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Oct 13, 2023 | - - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Apr 25, 2013 | - - |
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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Name
Calibrated prediction
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at