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NM_002778.4(PSAP):c.721-1G>C AND Sphingolipid activator protein 1 deficiency

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Dec 6, 2020
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV001973402.6

Allele description [Variation Report for NM_002778.4(PSAP):c.721-1G>C]

NM_002778.4(PSAP):c.721-1G>C

Gene:
PSAP:prosaposin [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
10q22.1
Genomic location:
Preferred name:
NM_002778.4(PSAP):c.721-1G>C
HGVS:
  • NC_000010.11:g.71825894C>G
  • NG_009301.1:g.30432G>C
  • NM_001042465.3:c.721-1G>C
  • NM_001042466.3:c.721-1G>C
  • NM_002778.4:c.721-1G>CMANE SELECT
  • NC_000010.10:g.73585651C>G
Links:
dbSNP: rs1842392331
NCBI 1000 Genomes Browser:
rs1842392331
Molecular consequence:
  • NM_001042465.3:c.721-1G>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001042466.3:c.721-1G>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_002778.4:c.721-1G>C - splice acceptor variant - [Sequence Ontology: SO:0001574]

Condition(s)

Name:
Sphingolipid activator protein 1 deficiency
Synonyms:
Metachromatic leukodystrophy due to saposin B deficiency; Metachromatic leukodystrophy due to cerebroside sulfatase activator deficiency; Saposin B Deficiency
Identifiers:
MONDO: MONDO:0009590; MedGen: C0268262; Orphanet: 512; OMIM: 249900

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002266411Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Likely pathogenic
(Dec 6, 2020) 		germlineclinical testing

PubMed (4)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Splicing in action: assessing disease causing sequence changes.

Baralle D, Baralle M.

J Med Genet. 2005 Oct;42(10):737-48. Review.

PubMed [citation]
PMID:
16199547
PMCID:
PMC1735933

A novel mutation in the coding region of the prosaposin gene leads to a complete deficiency of prosaposin and saposins, and is associated with a complex sphingolipidosis dominated by lactosylceramide accumulation.

Hulková H, Cervenková M, Ledvinová J, Tochácková M, Hrebícek M, Poupetová H, Befekadu A, Berná L, Paton BC, Harzer K, Böör A, Smíd F, Elleder M.

Hum Mol Genet. 2001 Apr 15;10(9):927-40.

PubMed [citation]
PMID:
11309366
See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002266411.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (4)

Description

In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This variant has not been reported in the literature in individuals with PSAP-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change affects an acceptor splice site in intron 6 of the PSAP gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in PSAP are known to be pathogenic (PMID: 11309366, 19267410).

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 29, 2024