rs757752213
Positions:
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 2P and 11B. PM2BP4_StrongBP6_ModerateBP7BS2
The ENST00000394936.8(PSAP):c.450C>T(p.His150=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,864 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: not found (cov: 32)
Exomes 𝑓: 0.0000034 ( 0 hom. )
Consequence
PSAP
ENST00000394936.8 synonymous
ENST00000394936.8 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.725
Genes affected
PSAP (HGNC:9498): (prosaposin) This gene encodes a highly conserved preproprotein that is proteolytically processed to generate four main cleavage products including saposins A, B, C, and D. Each domain of the precursor protein is approximately 80 amino acid residues long with nearly identical placement of cysteine residues and glycosylation sites. Saposins A-D localize primarily to the lysosomal compartment where they facilitate the catabolism of glycosphingolipids with short oligosaccharide groups. The precursor protein exists both as a secretory protein and as an integral membrane protein and has neurotrophic activities. Mutations in this gene have been associated with Gaucher disease and metachromatic leukodystrophy. Alternative splicing results in multiple transcript variants, at least one of which encodes an isoform that is proteolytically processed. [provided by RefSeq, Feb 2016]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -9 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.72).
BP6
Variant 10-71829003-G-A is Benign according to our data. Variant chr10-71829003-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2906807.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=0.725 with no splicing effect.
BS2
High AC in GnomAdExome4 at 5 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PSAP | NM_002778.4 | c.450C>T | p.His150= | synonymous_variant | 5/14 | ENST00000394936.8 | NP_002769.1 | |
PSAP | NM_001042465.3 | c.450C>T | p.His150= | synonymous_variant | 5/15 | NP_001035930.1 | ||
PSAP | NM_001042466.3 | c.450C>T | p.His150= | synonymous_variant | 5/15 | NP_001035931.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PSAP | ENST00000394936.8 | c.450C>T | p.His150= | synonymous_variant | 5/14 | 1 | NM_002778.4 | ENSP00000378394 | P1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD3 exomes AF: 0.0000119 AC: 3AN: 251426Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135908
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GnomAD4 exome AF: 0.00000342 AC: 5AN: 1461864Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3AN XY: 727240
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GnomAD4 genome Cov.: 32
GnomAD4 genome
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32
ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Sphingolipid activator protein 1 deficiency Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Oct 28, 2023 | - - |
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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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at