rs200965587
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Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 2P and 12B. PM2BP4_StrongBP6_Very_Strong
The NM_000391.4(TPP1):c.1426-10A>T variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000242 in 1,613,532 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00015 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000012 ( 0 hom. )
Consequence
TPP1
NM_000391.4 splice_polypyrimidine_tract, intron
NM_000391.4 splice_polypyrimidine_tract, intron
Scores
2
Splicing: ADA: 0.00006171
2
Clinical Significance
Conservation
PhyloP100: 0.828
Genes affected
TPP1 (HGNC:2073): (tripeptidyl peptidase 1) This gene encodes a member of the sedolisin family of serine proteases. The protease functions in the lysosome to cleave N-terminal tripeptides from substrates, and has weaker endopeptidase activity. It is synthesized as a catalytically-inactive enzyme which is activated and auto-proteolyzed upon acidification. Mutations in this gene result in late-infantile neuronal ceroid lipofuscinosis, which is associated with the failure to degrade specific neuropeptides and a subunit of ATP synthase in the lysosome. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -10 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.81).
BP6
?
Variant 11-6615001-T-A is Benign according to our data. Variant chr11-6615001-T-A is described in ClinVar as [Likely_benign]. Clinvar id is 457939.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TPP1 | NM_000391.4 | c.1426-10A>T | splice_polypyrimidine_tract_variant, intron_variant | ENST00000299427.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TPP1 | ENST00000299427.12 | c.1426-10A>T | splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_000391.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000145 AC: 22AN: 151544Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000358 AC: 9AN: 251470Hom.: 0 AF XY: 0.0000441 AC XY: 6AN XY: 135906
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GnomAD4 exome AF: 0.0000116 AC: 17AN: 1461870Hom.: 0 Cov.: 33 AF XY: 0.0000110 AC XY: 8AN XY: 727232
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GnomAD4 genome ? AF: 0.000145 AC: 22AN: 151662Hom.: 0 Cov.: 32 AF XY: 0.000162 AC XY: 12AN XY: 74138
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 15, 2021 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Nov 27, 2023 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at