rs755166149
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Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate
The NM_001171613.2(PREPL):c.1087-9C>G 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 0.00000317 in 1,575,140 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 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000028 ( 0 hom. )
Consequence
PREPL
NM_001171613.2 splice_polypyrimidine_tract, intron
NM_001171613.2 splice_polypyrimidine_tract, intron
Scores
2
Splicing: ADA: 0.002173
2
Clinical Significance
Conservation
PhyloP100: 1.63
Genes affected
PREPL (HGNC:30228): (prolyl endopeptidase like) The protein encoded by this gene belongs to the prolyl oligopeptidase subfamily of serine peptidases. Mutations in this gene have been associated with hypotonia-cystinuria syndrome, also known as the 2p21 deletion syndrome. Several alternatively spliced transcript variants encoding either the same or different isoforms have been described for this gene.[provided by RefSeq, Jan 2010]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -4 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.82).
BP6
?
Variant 2-44329121-G-C is Benign according to our data. Variant chr2-44329121-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 567457.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PREPL | NM_001171613.2 | c.1087-9C>G | splice_polypyrimidine_tract_variant, intron_variant | ENST00000409411.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PREPL | ENST00000409411.6 | c.1087-9C>G | splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_001171613.2 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152200Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000123 AC: 3AN: 244120Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 132046
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GnomAD4 exome AF: 0.00000281 AC: 4AN: 1422940Hom.: 0 Cov.: 30 AF XY: 0.00000423 AC XY: 3AN XY: 709608
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GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152200Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74346
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Myasthenic syndrome, congenital, 22 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Oct 24, 2022 | - - |
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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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