NM_000487.6(ARSA):c.1200C>T (p.Phe400=) AND Metachromatic leukodystrophy

Germline classification:: Likely pathogenic (2 submissions)
Last evaluated:: Jun 24, 2020
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:: RCV001250462.2

Allele description [Variation Report for NM_000487.6(ARSA):c.1200C>T (p.Phe400=)]

NM_000487.6(ARSA):c.1200C>T (p.Phe400=)

Gene:

ARSA:arylsulfatase A [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

22q13.33

Genomic location:

Preferred name:

NM_000487.6(ARSA):c.1200C>T (p.Phe400=)

Other names:

F400L

HGVS:

NC_000022.11:g.50625589G>A
NG_009260.2:g.7591C>T
NM_000487.6:c.1200C>TMANE SELECT
NM_001085425.3:c.1200C>T
NM_001085426.3:c.1200C>T
NM_001085427.3:c.1200C>T
NM_001085428.3:c.942C>T
NM_001362782.2:c.942C>T
NP_000478.3:p.Phe400=
NP_001078894.2:p.Phe400=
NP_001078895.2:p.Phe400=
NP_001078896.2:p.Phe400=
NP_001078897.1:p.Phe314=
NP_001349711.1:p.Phe314=
NC_000022.10:g.51064017G>A
NM_000487.5:c.1200C>T

Links:

dbSNP: rs1175674325

NCBI 1000 Genomes Browser:

rs1175674325

Molecular consequence:

NM_000487.6:c.1200C>T - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001085425.3:c.1200C>T - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001085426.3:c.1200C>T - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001085427.3:c.1200C>T - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001085428.3:c.942C>T - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001362782.2:c.942C>T - synonymous variant - [Sequence Ontology: SO:0001819]

Condition(s)

Name:: Metachromatic leukodystrophy (MLD)
Synonyms:: ARSA DEFICIENCY; CEREBROSIDE SULFATASE DEFICIENCY; METACHROMATIC LEUKOENCEPHALOPATHY; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0018868; MedGen: C0023522; Orphanet: 512; OMIM: 250100

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001424856	Amsterdam Leukodystrophy Center, Amsterdam UMC	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Jun 24, 2020)	inherited	clinical testing	PubMed (2) [See all records that cite these PMIDs] 25741868, 32632536
SCV001430136	Myelin Disorders Clinic-Children's Medical Center/Medical Genetics Lab-Tarbiat Modares University, Children's Medical Center, Pediatrics Center of Excellence,	no assertion criteria provided	Uncertain significance	inherited	clinical testing

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001424856

Amsterdam Leukodystrophy Center, Amsterdam UMC

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Jun 24, 2020)

inherited

clinical testing

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

SCV001430136

Myelin Disorders Clinic-Children's Medical Center/Medical Genetics Lab-Tarbiat Modares University, Children's Medical Center, Pediatrics Center of Excellence,

no assertion criteria provided

Uncertain significance

inherited

clinical testing

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	inherited	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
mixed ethnic group	inherited	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee.

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Metachromatic leukodystrophy genotypes in The Netherlands reveal novel pathogenic ARSA variants in non-Caucasian patients.

Beerepoot S, van Dooren SJM, Salomons GS, Boelens JJ, Jacobs EH, van der Knaap MS, van Kuilenburg ABP, Wolf NI.

Neurogenetics. 2020 Oct;21(4):289-299. doi: 10.1007/s10048-020-00621-6. Epub 2020 Jul 7.

PubMed [citation]

PMID:: 32632536
PMCID:: PMC7476914

Details of each submission

From Amsterdam Leukodystrophy Center, Amsterdam UMC, SCV001424856.1

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

Description

Homozygous - novel (late-juvenile MLD)

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

From Myelin Disorders Clinic-Children's Medical Center/Medical Genetics Lab-Tarbiat Modares University, Children's Medical Center, Pediatrics Center of Excellence,, SCV001430136.1

#	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	inherited	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Jan 13, 2025

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