NM_012434.5(SLC17A5):c.802_816del (p.Ser268_Asn272del) AND Salla disease

Germline classification:: Pathogenic (7 submissions)
Last evaluated:: Dec 28, 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:: RCV000049971.16

Allele description [Variation Report for NM_012434.5(SLC17A5):c.802_816del (p.Ser268_Asn272del)]

NM_012434.5(SLC17A5):c.802_816del (p.Ser268_Asn272del)

Gene:

SLC17A5:solute carrier family 17 member 5 [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

6q13

Genomic location:

Preferred name:

NM_012434.5(SLC17A5):c.802_816del (p.Ser268_Asn272del)

HGVS:

NC_000006.11:g.74345108_74345122del
NC_000006.12:g.73635386_73635400del
NG_008272.1:g.23616_23630del
NM_001382629.1:c.571_585del
NM_001382630.1:c.802_816del
NM_001382631.1:c.823_837del
NM_001382632.1:c.715_729del
NM_001382633.1:c.802_816del
NM_001382634.1:c.802_816del
NM_001382635.1:c.799_813del
NM_001382636.1:c.484_498del
NM_012434.5:c.802_816delMANE SELECT
NP_001369558.1:p.Ser191_Asn195del
NP_001369559.1:p.Ser268_Asn272del
NP_001369560.1:p.Ser275_Asn279del
NP_001369561.1:p.Ser239_Asn243del
NP_001369562.1:p.Ser268_Asn272del
NP_001369563.1:p.Ser268_Asn272del
NP_001369564.1:p.Ser267_Asn271del
NP_001369565.1:p.Ser162_Asn166del
NP_036566.1:p.Ser268_Asn272del
NC_000006.11:g.74345108_74345122del
NC_000006.11:g.74345109_74345123del
NC_000006.11:g.74345109_74345123delTTTCTTAATGATGAA
NM_012434.4:c.802_816delTCATCATTAAGAAAT
NM_012434.5:c.802_816delTCATCATTAAGAAATMANE SELECT

Links:

OMIM: 604322.0007; dbSNP: rs386833994

NCBI 1000 Genomes Browser:

rs386833994

Molecular consequence:

NM_001382629.1:c.571_585del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001382630.1:c.802_816del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001382631.1:c.823_837del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001382632.1:c.715_729del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001382633.1:c.802_816del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001382634.1:c.802_816del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001382635.1:c.799_813del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001382636.1:c.484_498del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_012434.5:c.802_816del - inframe_deletion - [Sequence Ontology: SO:0001822]

Condition(s)

Name:: Salla disease (SD)
Synonyms:: Sialuria, Finnish type; N-acetylneuraminic acid (NANA) storage disease (NSD); Infantile sialic acid storage disorder (ISSD); See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0011449; MedGen: C1096903; Orphanet: 309334; Orphanet: 834; OMIM: 604369

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000082380	Juha Muilu Group; Institute for Molecular Medicine Finland (FIMM)	no assertion criteria provided	probable-pathogenic	not provided	not provided	PubMed (1) [See all records that cite this PMID]
SCV000240033	OMIM	no assertion criteria provided	Pathogenic (Jul 1, 2003)	germline	literature only	PubMed (5) [See all records that cite these PMIDs] 10069709, 2334213, 12121352, 12794688, 10581036
SCV000699341	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Pathogenic (May 12, 2017)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 12359136, 15516337, 15805149, 10947946 LabCorp Variant Classification Summary - May 2015.docx, Citation Link,
SCV001163088	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Feb 6, 2024)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV001198532	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Dec 28, 2024)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 10581036, 12794688, 15805149, 12359136, 15510212, 28492532
SCV001453512	Natera, Inc.	no assertion criteria provided	Pathogenic (Sep 16, 2020)	germline	clinical testing
SCV002027575	Genome-Nilou Lab	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Sep 5, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Description

FinDis database variant: This variant was not found or characterized by our laboratory, data were collected from public sources: see reference: SCV000082380

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	no	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only
not provided	not provided	not provided	not provided	not provided	not provided	1	not provided	literature only
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Clinical spectrum of infantile free sialic acid storage disease.

Lemyre E, Russo P, Melançon SB, Gagné R, Potier M, Lambert M.

Am J Med Genet. 1999 Feb 19;82(5):385-91. Review.

PubMed [citation]

PMID:: 10069709

Sialic acid storage disease.

Cameron PD, Dubowitz V, Besley GT, Fensom AH.

Arch Dis Child. 1990 Mar;65(3):314-5.

PubMed [citation]

PMID:: 2334213
PMCID:: PMC1792249

See all PubMed Citations (12)

Details of each submission

From Juha Muilu Group; Institute for Molecular Medicine Finland (FIMM), SCV000082380.1

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

Description

Converted during submission to Likely pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	not provided	not provided	1	not provided	not provided		not provided	not provided	not provided	not provided

From OMIM, SCV000240033.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (5)

Description

In 2 French Canadian patients with infantile sialic acid storage disease (ISSD; 269920) reported by Lemyre et al. (1999) and in 1 English patient reported by Cameron et al. (1990), Verheijen et al. (1999) found a 15-bp deletion (nucleotides 802-816) resulting in the deletion of amino acids serine, serine, leucine, arginine, and asparagine in the cytosolic loop between transmembrane domains 6 and 7 of the SLC17A5 gene product.

Biancheri et al. (2002) described 2 Italian brothers with sialic acid storage disease that resembled Salla disease as observed in the Finnish population (SD; 604369) rather than ISSD. Both brothers showed moderate intellectual disability, spastic ataxic syndrome, hypomyelination and cerebellar ataxia on MRI, and lysosomal storage, all typical of Salla disease. In one of the alleles of the younger brother, Biancheri et al. (2002) found the same 15-bp deletion in exon 6 that had been found by Verheijen et al. (1999). No R39C mutation (604322.0001) was found. The older brother had died at the age of 20 years and DNA testing was not performed. The second mutation in the younger brother was presumed to lie in a noncoding area of the gene.

Kleta et al. (2003) detected this mutation in compound heterozygous state with an R39C substitution (604322.0001) in a North American patient with Salla disease. Kleta et al. (2003) described this mutation as 801 815del15 and stated that they believed the mutation detected by them was the same as that described by Verheijen et al. (1999).

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	not provided	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000699341.1

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

Description

Variant summary: The SLC17A5 c.802_816del15 (p.Ser268_Asn272del) variant causes an in-frame deletion in the cytosolic loop between TM domains 6 and 7 (Aula_2000). This variant was found in 2/119968 control chromosomes at a frequency of 0.0000167, which does not exceed the estimated maximal expected allele frequency of a pathogenic SLC17A5 variant (0.0023717). Multiple publications cite the variant in affected homozygous and compound heterozygous individuals diagnosed with ISSD. Functional studies found that due to this variant the ISSD polypeptide is mainly constrained to the Golgi compartment with limited presence in the lysosomes (Aula_2002) and also that it abrogates the transport activity of sialin (Wreden_2016) In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as pathogenic/likely pathogenic. Taken together, this variant is 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 Baylor Genetics, SCV001163088.2

#	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	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001198532.6

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

Description

This variant, c.802_816del, results in the deletion of 5 amino acid(s) of the SLC17A5 protein (p.Ser268_Asn272del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs386833994, gnomAD 0.006%). This variant has been observed in individual(s) with severe infantile sialic acid storage disease (PMID: 10581036, 12794688, 15805149). This variant is also known as 801-815del, SSLRN deletion, or "the ISSD deletion". ClinVar contains an entry for this variant (Variation ID: 56558). Algorithms developed to predict the effect of variants on gene product structure and function are not available or were not evaluated for this variant. Experimental studies have shown that this variant affects SLC17A5 function (PMID: 12359136, 15510212). 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 Natera, Inc., SCV001453512.1

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

#	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 Genome-Nilou Lab, SCV002027575.1

#	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	no	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Feb 25, 2025

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