NM_002778.4(PSAP):c.1076A>C (p.Glu359Ala) AND Sphingolipid activator protein 1 deficiency

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jan 15, 2024
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:: RCV002541741.3

Allele description [Variation Report for NM_002778.4(PSAP):c.1076A>C (p.Glu359Ala)]

NM_002778.4(PSAP):c.1076A>C (p.Glu359Ala)

Gene:

PSAP:prosaposin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

10q22.1

Genomic location:

Preferred name:

NM_002778.4(PSAP):c.1076A>C (p.Glu359Ala)

HGVS:

NC_000010.11:g.71819830T>G
NG_009301.1:g.36496A>C
NM_001042465.3:c.1085A>C
NM_001042466.3:c.1082A>C
NM_002778.4:c.1076A>CMANE SELECT
NP_001035930.1:p.Glu362Ala
NP_001035931.1:p.Glu361Ala
NP_002769.1:p.Glu359Ala
NC_000010.10:g.73579587T>G

Protein change:

E359A

Links:

dbSNP: rs765744298

NCBI 1000 Genomes Browser:

rs765744298

Molecular consequence:

NM_001042465.3:c.1085A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001042466.3:c.1082A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_002778.4:c.1076A>C - missense variant - [Sequence Ontology: SO:0001583]

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

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003473164	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 15, 2024)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 35456468, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003473164

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 15, 2024)

germline

clinical testing

PubMed (2)
[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

Phenotype Expansion for Atypical Gaucher Disease Due to Homozygous Missense PSAP Variant in a Large Consanguineous Pakistani Family.

Liaqat K, Hussain S, Acharya A, Nasir A, Bharadwaj T, Ansar M, Basit S, Schrauwen I, Ahmad W, Leal SM.

Genes (Basel). 2022 Apr 9;13(4). doi: 10.3390/genes13040662.

PubMed [citation]

PMID:: 35456468
PMCID:: PMC9028228

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group, Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9..

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003473164.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This sequence change replaces glutamic acid, which is acidic and polar, with alanine, which is neutral and non-polar, at codon 359 of the PSAP protein (p.Glu359Ala). This variant is present in population databases (rs765744298, gnomAD 0.04%). This missense change has been observed in individual(s) with atypical Gaucher disease (PMID: 35456468). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 991967). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on PSAP protein function. For these reasons, this variant has been classified as Pathogenic.

#	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

ClinVar

Relating variation to medicine