chr10-71819648-C-T
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_002778.4(PSAP):c.1193-26G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.187 in 1,613,892 control chromosomes in the GnomAD database, including 29,058 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.17 ( 2225 hom., cov: 32)
Exomes 𝑓: 0.19 ( 26833 hom. )
Consequence
PSAP
NM_002778.4 intron
NM_002778.4 intron
Scores
2
Clinical Significance
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 -20 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.84).
BP6
Variant 10-71819648-C-T is Benign according to our data. Variant chr10-71819648-C-T is described in ClinVar as [Benign]. Clinvar id is 258808.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.237 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PSAP | NM_002778.4 | c.1193-26G>A | intron_variant | ENST00000394936.8 | |||
PSAP | NM_001042465.3 | c.1202-26G>A | intron_variant | ||||
PSAP | NM_001042466.3 | c.1199-26G>A | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PSAP | ENST00000394936.8 | c.1193-26G>A | intron_variant | 1 | NM_002778.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.167 AC: 25442AN: 152032Hom.: 2225 Cov.: 32
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GnomAD3 exomes AF: 0.174 AC: 43711AN: 250966Hom.: 4057 AF XY: 0.173 AC XY: 23475AN XY: 135690
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GnomAD4 exome AF: 0.189 AC: 275872AN: 1461740Hom.: 26833 Cov.: 38 AF XY: 0.186 AC XY: 135561AN XY: 727170
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GnomAD4 genome AF: 0.167 AC: 25446AN: 152152Hom.: 2225 Cov.: 32 AF XY: 0.168 AC XY: 12520AN XY: 74386
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ClinVar
Significance: Benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Combined PSAP deficiency Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 10, 2021 | - - |
Krabbe disease due to saposin A deficiency Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 10, 2021 | - - |
not provided Benign:1
Benign, no assertion criteria provided | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | Oct 22, 2015 | - - |
Sphingolipid activator protein 1 deficiency Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 10, 2021 | - - |
Computational scores
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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