rs2289145
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_001077446.4(TSEN34):c.*29G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.01 in 1,613,706 control chromosomes in the GnomAD database, including 737 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.024 ( 117 hom., cov: 32)
Exomes 𝑓: 0.0086 ( 620 hom. )
Consequence
TSEN34
NM_001077446.4 3_prime_UTR
NM_001077446.4 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.113
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 -20 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.83).
BP6
?
Variant 19-54193391-G-A is Benign according to our data. Variant chr19-54193391-G-A is described in ClinVar as [Benign]. Clinvar id is 261679.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
?
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.124 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TSEN34 | NM_001077446.4 | c.*29G>A | 3_prime_UTR_variant | 4/4 | ENST00000396388.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TSEN34 | ENST00000396388.3 | c.*29G>A | 3_prime_UTR_variant | 4/4 | 1 | NM_001077446.4 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.0238 AC: 3625AN: 152166Hom.: 117 Cov.: 32
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GnomAD3 exomes AF: 0.0211 AC: 5234AN: 248252Hom.: 226 AF XY: 0.0178 AC XY: 2401AN XY: 134758
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GnomAD4 exome AF: 0.00856 AC: 12509AN: 1461422Hom.: 620 Cov.: 33 AF XY: 0.00811 AC XY: 5895AN XY: 726970
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GnomAD4 genome ? AF: 0.0239 AC: 3638AN: 152284Hom.: 117 Cov.: 32 AF XY: 0.0250 AC XY: 1863AN XY: 74460
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ClinVar
Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 06, 2018 | - - |
Pontoneocerebellar hypoplasia Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 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
Benign
DANN
Benign
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