NM_003896.4(ST3GAL5):c.318+1del AND GM3 synthase deficiency

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Dec 3, 2019
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:: RCV001244482.6

Allele description [Variation Report for NM_003896.4(ST3GAL5):c.318+1del]

NM_003896.4(ST3GAL5):c.318+1del

Gene:

ST3GAL5:ST3 beta-galactoside alpha-2,3-sialyltransferase 5 [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

2p11.2

Genomic location:

Preferred name:

NM_003896.4(ST3GAL5):c.318+1del

HGVS:

NC_000002.12:g.85861181del
NG_012807.1:g.32855del
NG_012807.2:g.32854del
NM_001042437.2:c.249+1del
NM_001354223.2:c.-244+1del
NM_001354224.2:c.-307+1del
NM_001354226.2:c.-244+1del
NM_001354227.2:c.234+1del
NM_001354229.2:c.234+1del
NM_001354233.2:c.-684+1del
NM_001354234.1:c.-648+1del
NM_001354238.1:c.234+1del
NM_001363847.1:c.318+1del
NM_003896.4:c.318+1delMANE SELECT
NC_000002.11:g.86088303del
NC_000002.11:g.86088304del
NM_003896.3:c.318del

Links:

dbSNP: rs1684687070

NCBI 1000 Genomes Browser:

rs1684687070

Molecular consequence:

NM_001042437.2:c.249+1del - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001354223.2:c.-244+1del - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001354224.2:c.-307+1del - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001354226.2:c.-244+1del - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001354227.2:c.234+1del - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001354229.2:c.234+1del - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001354233.2:c.-684+1del - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001354234.1:c.-648+1del - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001354238.1:c.234+1del - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001363847.1:c.318+1del - splice donor variant - [Sequence Ontology: SO:0001575]
NM_003896.4:c.318+1del - splice donor variant - [Sequence Ontology: SO:0001575]

Condition(s)

Name:: GM3 synthase deficiency (SPDRS)
Synonyms:: SALT AND PEPPER MENTAL RETARDATION SYNDROME; Salt and pepper developmental regression syndrome; Salt and pepper syndrome
Identifiers:: MONDO: MONDO:0018274; MedGen: C1836824; Orphanet: 171714; OMIM: 609056

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001417704	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Dec 3, 2019)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 15502825, 22990144, 27232954, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001417704

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Dec 3, 2019)

germline

clinical testing

PubMed (4)
[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

Infantile-onset symptomatic epilepsy syndrome caused by a homozygous loss-of-function mutation of GM3 synthase.

Simpson MA, Cross H, Proukakis C, Priestman DA, Neville DC, Reinkensmeier G, Wang H, Wiznitzer M, Gurtz K, Verganelaki A, Pryde A, Patton MA, Dwek RA, Butters TD, Platt FM, Crosby AH.

Nat Genet. 2004 Nov;36(11):1225-9. Epub 2004 Oct 24.

PubMed [citation]

PMID:: 15502825

Refractory epilepsy and mitochondrial dysfunction due to GM3 synthase deficiency.

Fragaki K, Ait-El-Mkadem S, Chaussenot A, Gire C, Mengual R, Bonesso L, Bénéteau M, Ricci JE, Desquiret-Dumas V, Procaccio V, Rötig A, Paquis-Flucklinger V.

Eur J Hum Genet. 2013 May;21(5):528-34. doi: 10.1038/ejhg.2012.202. Epub 2012 Sep 19.

PubMed [citation]

PMID:: 22990144
PMCID:: PMC3641379

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001417704.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in ST3GAL5 are known to be pathogenic (PMID: 15502825, 22990144, 27232954). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. This variant has not been reported in the literature in individuals with ST3GAL5-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.?) in the ST3GAL5 gene. It is expected to result in an absent or disrupted protein product.

#	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: Sep 29, 2024

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