rs11559205
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Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1
The NM_207346.3(TSEN54):āc.409A>Cā(p.Ile137Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0724 in 1,613,612 control chromosomes in the GnomAD database, including 5,068 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā ā ).
Frequency
Genomes: š 0.097 ( 975 hom., cov: 32)
Exomes š: 0.070 ( 4093 hom. )
Consequence
TSEN54
NM_207346.3 missense
NM_207346.3 missense
Scores
3
13
Clinical Significance
Conservation
PhyloP100: 1.54
Genes affected
TSEN54 (HGNC:27561): (tRNA splicing endonuclease subunit 54) This gene encodes a subunit of the tRNA splicing endonuclease complex, which catalyzes the removal of introns from precursor tRNAs. The complex is also implicated in pre-mRNA 3-prime end processing. Mutations in this gene result in pontocerebellar hypoplasia type 2.[provided by RefSeq, Oct 2009]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -16 ACMG points.
BP6
?
Variant 17-75517596-A-C is Benign according to our data. Variant chr17-75517596-A-C is described in ClinVar as [Benign]. Clinvar id is 160134.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-75517596-A-C is described in Lovd as [Benign].
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.172 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TSEN54 | NM_207346.3 | c.409A>C | p.Ile137Leu | missense_variant | 5/11 | ENST00000333213.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TSEN54 | ENST00000333213.11 | c.409A>C | p.Ile137Leu | missense_variant | 5/11 | 1 | NM_207346.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0969 AC: 14715AN: 151824Hom.: 970 Cov.: 32
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GnomAD3 exomes AF: 0.0726 AC: 18249AN: 251400Hom.: 844 AF XY: 0.0727 AC XY: 9876AN XY: 135878
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GnomAD4 exome AF: 0.0699 AC: 102154AN: 1461670Hom.: 4093 Cov.: 33 AF XY: 0.0702 AC XY: 51078AN XY: 727118
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GnomAD4 genome ? AF: 0.0970 AC: 14738AN: 151942Hom.: 975 Cov.: 32 AF XY: 0.0959 AC XY: 7118AN XY: 74250
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ESP6500AA
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ClinVar
Significance: Benign
Submissions summary: Benign:12
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:5
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Feb 08, 2013 | - - |
Benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Pontocerebellar hypoplasia type 2A Benign:2
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Sep 10, 2021 | - - |
Benign, criteria provided, single submitter | clinical testing | Victorian Clinical Genetics Services, Murdoch Childrens Research Institute | Oct 19, 2020 | Based on the classification scheme VCGS_Germline_v1.3.3, this variant is classified as Benign. Following criteria are met: 0102 - Loss of function is a likely mechanism of disease in this gene and is associated with pontocerebellar hypoplasia type 2A (MIM#277470) and type 4 (MIM#225753). (I) 0106 - This gene is associated with autosomal recessive disease. (I) 0200 - Variant is predicted to result in a missense amino acid change from isoleucine to leucine. (I) 0251 - This variant is heterozygous. (I) 0307 - Variant is present in gnomAD (v2) at a frequency >=0.05 (19200 heterozygotes, 1035 homozygotes). (SB) 0503 - Missense variant consistently predicted to be tolerated by multiple in silico tools or not conserved in placental mammals with a minor amino acid change. (SB) 0600 - Variant is located in the annotated endA superfamily domain (NCBI Conserved Domain). (I) 0805 - This variant has strong previous evidence of being benign in unrelated individuals. (ClinVar). (SB) 1208 - Inheritance information for this variant is not currently available in this individual. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign - |
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 03, 2015 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | 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. - |
Pontocerebellar hypoplasia type 5 Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Sep 10, 2021 | - - |
Pontocerebellar hypoplasia type 4 Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Sep 10, 2021 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Benign
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationTaster
Benign
P
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Benign
T;D
Sift4G
Benign
T;D
Polyphen
0.97
.;D
Vest4
0.18
MPC
0.37
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_AG_spliceai
Position offset: 6
Find out detailed SpliceAI scores and Pangolin per-transcript scores at