NM_002778.4(PSAP):c.1066G>T (p.Glu356Ter) AND Sphingolipid activator protein 1 deficiency

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Mar 16, 2023
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:: RCV003628471.2

Allele description [Variation Report for NM_002778.4(PSAP):c.1066G>T (p.Glu356Ter)]

NM_002778.4(PSAP):c.1066G>T (p.Glu356Ter)

Gene:

PSAP:prosaposin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

10q22.1

Genomic location:

Preferred name:

NM_002778.4(PSAP):c.1066G>T (p.Glu356Ter)

HGVS:

NC_000010.11:g.71819840C>A
NG_009301.1:g.36486G>T
NM_001042465.3:c.1075G>T
NM_001042466.3:c.1072G>T
NM_002778.4:c.1066G>TMANE SELECT
NP_001035930.1:p.Glu359Ter
NP_001035931.1:p.Glu358Ter
NP_002769.1:p.Glu356Ter
NC_000010.10:g.73579597C>A

Protein change:

E356*

Molecular consequence:

NM_001042465.3:c.1075G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001042466.3:c.1072G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_002778.4:c.1066G>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Sphingolipid activator protein 1 deficiency
Synonyms:: METACHROMATIC LEUKODYSTROPHY DUE TO CEREBROSIDE SULFATASE ACTIVATOR DEFICIENCY; Metachromatic leukodystrophy due to saposin B deficiency; Saposin B Deficiency
Identifiers:: MONDO: MONDO:0009590; MedGen: C0268262; Orphanet: 512; OMIM: 249900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004446015	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Mar 16, 2023)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 8554069, 11309366, 17616409, 19267410, 30632081, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004446015

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Mar 16, 2023)

germline

clinical testing

PubMed (6)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Analysis of a splice-site mutation in the sap-precursor gene of a patient with metachromatic leukodystrophy.

Henseler M, Klein A, Reber M, Vanier MT, Landrieu P, Sandhoff K.

Am J Hum Genet. 1996 Jan;58(1):65-74.

PubMed [citation]

PMID:: 8554069
PMCID:: PMC1914953

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 (6)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004446015.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (6)

Description

For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with PSAP-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Glu356*) in the PSAP gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PSAP are known to be pathogenic (PMID: 8554069, 11309366, 17616409, 19267410, 30632081).

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Jan 13, 2025

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