NM_000046.5(ARSB):c.1052C>T (p.Ser351Phe) AND Mucopolysaccharidosis type 6

Germline classification:: Likely pathogenic (3 submissions)
Last evaluated:: Mar 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:: RCV000677443.5

Allele description [Variation Report for NM_000046.5(ARSB):c.1052C>T (p.Ser351Phe)]

NM_000046.5(ARSB):c.1052C>T (p.Ser351Phe)

Gene:

ARSB:arylsulfatase B [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

5q14.1

Genomic location:

Preferred name:

NM_000046.5(ARSB):c.1052C>T (p.Ser351Phe)

HGVS:

NC_000005.10:g.78885674G>A
NG_007089.1:g.105861C>T
NM_000046.3:c.1052C>T
NM_000046.5:c.1052C>TMANE SELECT
NM_198709.3:c.1052C>T
NP_000037.2:p.Ser351Phe
NP_942002.1:p.Ser351Phe
NC_000005.9:g.78181497G>A
NM_000046.4:c.1052C>T
NM_000046.5:c.1052C>T

Protein change:

S351F

Links:

dbSNP: rs756671977

NCBI 1000 Genomes Browser:

rs756671977

Molecular consequence:

NM_000046.5:c.1052C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_198709.3:c.1052C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Mucopolysaccharidosis type 6 (MPS6)
Synonyms:: MPS VI; Mucopolysaccharidosis type VI; MPS 6; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0009661; MedGen: C0026709; Orphanet: 583; OMIM: 253200

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000802945	Laboratory of Diagnosis and Therapy of Lysosomal Disorders, University of Padova	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Jan 1, 2018)	germline	curation	PubMed (3) [See all records that cite these PMIDs] 22976768, 25741868, 30118150
SCV002317008	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Jan 4, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 22976768, 28492532
SCV005055414	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Mar 28, 2024)	unknown	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

SCV000802945

Laboratory of Diagnosis and Therapy of Lysosomal Disorders, University of Padova

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Jan 1, 2018)

germline

curation

PubMed (3)
[See all records that cite these PMIDs]

SCV002317008

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Jan 4, 2022)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

SCV005055414

Baylor Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Mar 28, 2024)

unknown

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	yes	not provided	not provided	not provided	not provided	not provided	curation
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

Mucopolysaccharidosis type VI (MPS VI) and molecular analysis: Review and classification of published variants in the ARSB gene.

Tomanin R, Karageorgos L, Zanetti A, Al-Sayed M, Bailey M, Miller N, Sakuraba H, Hopwood JJ.

Hum Mutat. 2018 Dec;39(12):1788-1802. doi: 10.1002/humu.23613. Epub 2018 Sep 17. Review.

PubMed [citation]

PMID:: 30118150
PMCID:: PMC6282714

Molecular characterization of 355 mucopolysaccharidosis patients reveals 104 novel mutations.

Pollard LM, Jones JR, Wood TC.

J Inherit Metab Dis. 2013 Mar;36(2):179-87. doi: 10.1007/s10545-012-9533-7. Epub 2012 Sep 14.

PubMed [citation]

PMID:: 22976768

See all PubMed Citations (4)

Details of each submission

From Laboratory of Diagnosis and Therapy of Lysosomal Disorders, University of Padova, SCV000802945.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	curation	PubMed (3)

Description

In vitro functional studies supportive of a damaging effect on the gene product (low to no ARSB activity in homozygotes; PS3);Very low frequency in ExAC (PM2)

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

From Invitae, SCV002317008.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt ARSB protein function. ClinVar contains an entry for this variant (Variation ID: 559669). This missense change has been observed in individual(s) with ARSB-related conditions (PMID: 22976768). This variant is present in population databases (rs756671977, gnomAD 0.003%). This sequence change replaces serine, which is neutral and polar, with phenylalanine, which is neutral and non-polar, at codon 351 of the ARSB protein (p.Ser351Phe).

#	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, SCV005055414.1

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

Last Updated: Jun 17, 2024

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