NM_003896.4(ST3GAL5):c.1008+1G>A AND GM3 synthase deficiency

This record was updated by the submitter. Please see the current version.

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Dec 11, 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:: RCV003614488.1

Allele description

NM_003896.4(ST3GAL5):c.1008+1G>A

Gene:

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

Variant type:

single nucleotide variant

Cytogenetic location:

2p11.2

Genomic location:

Preferred name:

NM_003896.4(ST3GAL5):c.1008+1G>A

HGVS:

NC_000002.12:g.85844395C>T
NG_012807.1:g.49640G>A
NG_012807.2:g.49639G>A
NM_001042437.2:c.939+1G>A
NM_001354223.2:c.624+1G>A
NM_001354224.2:c.624+1G>A
NM_001354226.2:c.624+1G>A
NM_001354227.2:c.924+1G>A
NM_001354229.2:c.924+1G>A
NM_001354233.2:c.624+1G>A
NM_001354234.1:c.624+1G>A
NM_001354238.1:c.924+1G>A
NM_001354247.1:c.285+1G>A
NM_001354248.1:c.624+1G>A
NM_001363847.1:c.849+1982G>A
NM_003896.4:c.1008+1G>AMANE SELECT
NC_000002.11:g.86071518C>T

Molecular consequence:

NM_001363847.1:c.849+1982G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001042437.2:c.939+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001354223.2:c.624+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001354224.2:c.624+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001354226.2:c.624+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001354227.2:c.924+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001354229.2:c.924+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001354233.2:c.624+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001354234.1:c.624+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001354238.1:c.924+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001354247.1:c.285+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001354248.1:c.624+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_003896.4:c.1008+1G>A - 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
SCV004396581	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Dec 11, 2023)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 17576681, 9536098, 30576498, 32404165, 34906476, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004396581

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Dec 11, 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

Aberrant 5' splice sites in human disease genes: mutation pattern, nucleotide structure and comparison of computational tools that predict their utilization.

Buratti E, Chivers M, Královicová J, Romano M, Baralle M, Krainer AR, Vorechovsky I.

Nucleic Acids Res. 2007;35(13):4250-63. Epub 2007 Jun 18.

PubMed [citation]

PMID:: 17576681
PMCID:: PMC1934990

Statistical features of human exons and their flanking regions.

Zhang MQ.

Hum Mol Genet. 1998 May;7(5):919-32.

PubMed [citation]

PMID:: 9536098

See all PubMed Citations (6)

Details of each submission

From Invitae, SCV004396581.1

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

Description

This sequence change affects a donor splice site in intron 6 of the ST3GAL5 gene. While this variant is not anticipated to result in nonsense mediated decay, it likely alters RNA splicing and results in a disrupted protein product. 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. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. This variant disrupts a region of the ST3GAL5 protein in which other variant(s) (p.Gly342Ser) have been determined to be pathogenic (PMID: 30576498, 32404165, 34906476). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. 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: Feb 28, 2024

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