NM_003896.4(ST3GAL5):c.353del (p.Lys118fs) AND GM3 synthase deficiency

Germline classification:: Pathogenic/Likely pathogenic (2 submissions)
Last evaluated:: Jan 26, 2024
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000700158.8

Allele description [Variation Report for NM_003896.4(ST3GAL5):c.353del (p.Lys118fs)]

NM_003896.4(ST3GAL5):c.353del (p.Lys118fs)

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.353del (p.Lys118fs)

HGVS:

NC_000002.12:g.85848171del
NG_012807.1:g.45865del
NM_001042437.2:c.284del
NM_001354223.2:c.-32del
NM_001354224.2:c.-32del
NM_001354226.2:c.-32del
NM_001354227.2:c.269del
NM_001354229.2:c.269del
NM_001354233.2:c.-32del
NM_001354234.1:c.-32del
NM_001354238.1:c.269del
NM_001354247.1:c.-552del
NM_001354248.1:c.-32del
NM_001363847.1:c.353del
NM_003896.4:c.353delMANE SELECT
NP_001035902.1:p.Lys95fs
NP_001341156.1:p.Lys90fs
NP_001341158.1:p.Lys90fs
NP_001341167.1:p.Lys90fs
NP_001350776.1:p.Lys118fs
NP_003887.3:p.Lys118fs
NC_000002.11:g.86075293del
NC_000002.11:g.86075294del
NM_003896.3:c.353delA

Protein change:

K118fs

Links:

dbSNP: rs754643632

NCBI 1000 Genomes Browser:

rs754643632

Molecular consequence:

NM_001354223.2:c.-32del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354224.2:c.-32del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354226.2:c.-32del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354233.2:c.-32del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354234.1:c.-32del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354247.1:c.-552del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354248.1:c.-32del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001042437.2:c.284del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354227.2:c.269del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354229.2:c.269del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354238.1:c.269del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001363847.1:c.353del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_003896.4:c.353del - frameshift variant - [Sequence Ontology: SO:0001589]

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
SCV000828903	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 26, 2024)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 15502825, 22990144, 27232954, 28492532
SCV002023668	Revvity Omics, Revvity	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Dec 5, 2019)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000828903

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 26, 2024)

germline

clinical testing

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

SCV002023668

Revvity Omics, Revvity

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Dec 5, 2019)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

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 (5)

Details of each submission

From Invitae, SCV000828903.4

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

Description

This sequence change creates a premature translational stop signal (p.Lys118Argfs*70) in the ST3GAL5 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ST3GAL5 are known to be pathogenic (PMID: 15502825, 22990144, 27232954). This variant is present in population databases (rs754643632, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with ST3GAL5-related conditions. ClinVar contains an entry for this variant (Variation ID: 577410). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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

From Revvity Omics, Revvity, SCV002023668.3

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

#	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: Jun 17, 2024

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