10-71819648-C-G
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Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_002778.4(PSAP):c.1193-26G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000322 in 1,614,002 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000032 ( 0 hom. )
Consequence
PSAP
NM_002778.4 intron
NM_002778.4 intron
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -3.62
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 -8 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.83).
BS2
High AC in GnomAd4 at 5 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PSAP | NM_002778.4 | c.1193-26G>C | intron_variant | ENST00000394936.8 | |||
PSAP | NM_001042465.3 | c.1202-26G>C | intron_variant | ||||
PSAP | NM_001042466.3 | c.1199-26G>C | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PSAP | ENST00000394936.8 | c.1193-26G>C | intron_variant | 1 | NM_002778.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000329 AC: 5AN: 152078Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000558 AC: 14AN: 250966Hom.: 0 AF XY: 0.0000368 AC XY: 5AN XY: 135690
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GnomAD4 exome AF: 0.0000322 AC: 47AN: 1461804Hom.: 0 Cov.: 38 AF XY: 0.0000358 AC XY: 26AN XY: 727200
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GnomAD4 genome AF: 0.0000329 AC: 5AN: 152198Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74406
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ClinVar
Not reported inComputational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at