NM_003896.4(ST3GAL5):c.998del (p.Gly333fs) AND GM3 synthase deficiency

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Sep 27, 2022
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:: RCV002607588.2

Allele description [Variation Report for NM_003896.4(ST3GAL5):c.998del (p.Gly333fs)]

NM_003896.4(ST3GAL5):c.998del (p.Gly333fs)

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.998del (p.Gly333fs)

HGVS:

NC_000002.12:g.85844409del
NG_012807.2:g.49628del
NM_001042437.2:c.929del
NM_001354223.2:c.614del
NM_001354224.2:c.614del
NM_001354226.2:c.614del
NM_001354227.2:c.914del
NM_001354229.2:c.914del
NM_001354233.2:c.614del
NM_001354234.1:c.614del
NM_001354238.1:c.914del
NM_001354247.1:c.275del
NM_001354248.1:c.614del
NM_001363847.1:c.849+1971del
NM_003896.4:c.998delMANE SELECT
NP_001035902.1:p.Gly310fs
NP_001341152.1:p.Gly205fs
NP_001341153.1:p.Gly205fs
NP_001341155.1:p.Gly205fs
NP_001341156.1:p.Gly305fs
NP_001341158.1:p.Gly305fs
NP_001341162.1:p.Gly205fs
NP_001341163.1:p.Gly205fs
NP_001341167.1:p.Gly305fs
NP_001341176.1:p.Gly92fs
NP_001341177.1:p.Gly205fs
NP_003887.3:p.Gly333fs
NC_000002.11:g.86071529del
NC_000002.11:g.86071532del
NG_012807.1:g.49629del

Protein change:

G205fs

Molecular consequence:

NM_001042437.2:c.929del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354223.2:c.614del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354224.2:c.614del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354226.2:c.614del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354227.2:c.914del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354229.2:c.914del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354233.2:c.614del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354234.1:c.614del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354238.1:c.914del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354247.1:c.275del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354248.1:c.614del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_003896.4:c.998del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001363847.1:c.849+1971del - intron variant - [Sequence Ontology: SO:0001627]

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

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
SCV003511270	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Sep 27, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 30576498, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003511270

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Sep 27, 2022)

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

Total loss of GM3 synthase activity by a normally processed enzyme in a novel variant and in all ST3GAL5 variants reported to cause a distinct congenital disorder of glycosylation.

Indellicato R, Parini R, Domenighini R, Malagolini N, Iascone M, Gasperini S, Masera N, dall'Olio F, Trinchera M.

Glycobiology. 2019 Mar 1;29(3):229-241. doi: 10.1093/glycob/cwy112.

PubMed [citation]

PMID:: 30576498

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, SCV003511270.1

#	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 creates a premature translational stop signal (p.Gly333Alafs*16) in the ST3GAL5 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 86 amino acid(s) of the ST3GAL5 protein. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with ST3GAL5-related conditions. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. This variant disrupts a region of the ST3GAL5 protein in which other variant(s) (p.Gly342Ser) have been observed in individuals with ST3GAL5-related conditions (PMID: 30576498). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#	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

ClinVar

Relating variation to medicine