NM_000046.5(ARSB):c.1151G>A (p.Ser384Asn) AND Mucopolysaccharidosis type 6

Germline classification:: Benign (5 submissions)
Last evaluated:: Feb 1, 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:: RCV000261664.24

Allele description [Variation Report for NM_000046.5(ARSB):c.1151G>A (p.Ser384Asn)]

NM_000046.5(ARSB):c.1151G>A (p.Ser384Asn)

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.1151G>A (p.Ser384Asn)

Other names:

NM_000046.3(ARSB):c.1151G>A(p.Ser384Asn); NM_198709.2(ARSB):c.1151G>A(p.Ser384Asn)

HGVS:

NC_000005.10:g.78839418C>T
NG_007089.1:g.152117G>A
NM_000046.5:c.1151G>AMANE SELECT
NM_198709.3:c.1151G>A
NP_000037.2:p.Ser384Asn
NP_000037.2:p.Ser384Asn
NP_942002.1:p.Ser384Asn
NC_000005.9:g.78135241C>T
NM_000046.3:c.1151G>A
NM_000046.4:c.1151G>A
P15848:p.Ser384Asn

Protein change:

S384N

Links:

UniProtKB: P15848#VAR_019030; dbSNP: rs25414

NCBI 1000 Genomes Browser:

rs25414

Molecular consequence:

NM_000046.5:c.1151G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_198709.3:c.1151G>A - 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
SCV000458380	Illumina Laboratory Services, Illumina	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019)	Benign (Mar 6, 2018)	germline	clinical testing	Citation Link,
SCV000802961	Laboratory of Diagnosis and Therapy of Lysosomal Disorders, University of Padova	criteria provided, single submitter (ACMG Guidelines, 2015)	Benign (Jan 1, 2018)	germline	curation	PubMed (8) [See all records that cite these PMIDs] 17161971, 10923267, 14974081, 16435196, 24875751, 19259130, 25741868, 30118150
SCV000803562	SIB Swiss Institute of Bioinformatics	criteria provided, single submitter (ACMG Guidelines, 2015)	Benign (May 31, 2018)	unknown	curation	PubMed (2) [See all records that cite these PMIDs] 19259130, 25741868
SCV001729375	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Benign (Feb 1, 2024)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002084968	Natera, Inc.	no assertion criteria provided	Benign (Nov 5, 2019)	germline	clinical testing

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	curation
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

Citations

PubMed

Mutational analysis of mucopolysaccharidosis type VI patients undergoing a phase II trial of enzyme replacement therapy.

Karageorgos L, Brooks DA, Harmatz P, Ketteridge D, Pollard A, Melville EL, Parkinson-Lawrence E, Clements PR, Hopwood JJ.

Mol Genet Metab. 2007 Feb;90(2):164-70. Epub 2006 Dec 11.

PubMed [citation]

PMID:: 17161971

[Identification of mutations in the arylsulfatase B gene in Russian mucopolysaccharidosis type VI patients].

Voskoboeva EIu, Krasnopol'skaia KD, Peters K, von Figura K.

Genetika. 2000 Jun;36(6):837-43. Russian.

PubMed [citation]

PMID:: 10923267

See all PubMed Citations (9)

Details of each submission

From Illumina Laboratory Services, Illumina, SCV000458380.3

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

Description

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.

#	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 Laboratory of Diagnosis and Therapy of Lysosomal Disorders, University of Padova, SCV000802961.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	curation	PubMed (8)

Description

Allele frequency greater than expected for disorder (BS1); Homozygotes reported in ExAC (BS2); Classified benign by a reputable source (BP6)

#	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 SIB Swiss Institute of Bioinformatics, SCV000803562.1

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

Description

This variant is interpreted as a Benign, for Mucopolysaccharidosis type VI, in Autosomal Recessive manner. The following ACMG Tag(s) were applied: BS1 => Allele frequency is greater than expected for disorder. BS2 => Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age. BP4 => Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.). BS4 => Lack of segregation in affected members of a family (PMID:19259130).

#	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, SCV001729375.4

#	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

From Natera, Inc., SCV002084968.1

#	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

Last Updated: Nov 30, 2024

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