chr19-54191191-G-C
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2
The ENST00000302937.8(TSEN34):c.-4-170G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00121 in 1,387,238 control chromosomes in the GnomAD database, including 23 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.0064 ( 16 hom., cov: 33)
Exomes 𝑓: 0.00057 ( 7 hom. )
Consequence
TSEN34
ENST00000302937.8 intron
ENST00000302937.8 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 2.42
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 -14 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.7).
BP6
?
Variant 19-54191191-G-C is Benign according to our data. Variant chr19-54191191-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 1194740.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00637 (970/152214) while in subpopulation AFR AF= 0.0213 (887/41552). AF 95% confidence interval is 0.0202. There are 16 homozygotes in gnomad4. There are 481 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd at 16 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TSEN34 | NM_001282332.2 | c.-5+154G>C | intron_variant | ||||
TSEN34 | NM_001282333.2 | c.-4-170G>C | intron_variant | ||||
TSEN34 | NM_001386740.1 | c.-4-170G>C | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TSEN34 | ENST00000302937.8 | c.-4-170G>C | intron_variant | 1 | P2 | ||||
TSEN34 | ENST00000396383.5 | c.-5+154G>C | intron_variant | 1 | P2 | ||||
TSEN34 | ENST00000429671.7 | c.-4-170G>C | intron_variant | 2 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.00636 AC: 968AN: 152098Hom.: 16 Cov.: 33
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GnomAD4 exome AF: 0.000572 AC: 706AN: 1235024Hom.: 7 Cov.: 33 AF XY: 0.000558 AC XY: 334AN XY: 599018
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GnomAD4 genome ? AF: 0.00637 AC: 970AN: 152214Hom.: 16 Cov.: 33 AF XY: 0.00646 AC XY: 481AN XY: 74422
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | May 14, 2019 | - - |
Computational scores
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at