NM_000487.6(ARSA):c.769G>C (p.Asp257His) AND not provided

Germline classification:: Pathogenic (3 submissions)
Last evaluated:: Mar 19, 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:: RCV000255092.10

Allele description [Variation Report for NM_000487.6(ARSA):c.769G>C (p.Asp257His)]

NM_000487.6(ARSA):c.769G>C (p.Asp257His)

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.769G>C (p.Asp257His)

Other names:

p.Asp257His

HGVS:

NC_000022.11:g.50626676C>G
NG_009260.2:g.6504G>C
NM_000487.6:c.769G>CMANE SELECT
NM_001085425.3:c.769G>C
NM_001085426.3:c.769G>C
NM_001085427.3:c.769G>C
NM_001085428.3:c.511G>C
NM_001362782.2:c.511G>C
NP_000478.3:p.Asp257His
NP_001078894.2:p.Asp257His
NP_001078895.2:p.Asp257His
NP_001078896.2:p.Asp257His
NP_001078897.1:p.Asp171His
NP_001349711.1:p.Asp171His
NC_000022.10:g.51065104C>G
NM_000487.4:c.763G>C
NM_000487.5:c.769G>C

Protein change:

D171H

Links:

dbSNP: rs80338819

NCBI 1000 Genomes Browser:

rs80338819

Molecular consequence:

NM_000487.6:c.769G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001085425.3:c.769G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001085426.3:c.769G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001085427.3:c.769G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001085428.3:c.511G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001362782.2:c.511G>C - missense variant - [Sequence Ontology: SO:0001583]

Functional consequence:

loss_of_function_variant [Sequence Ontology: SO:0002054] - Comment(s)

Observations:

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000322398	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Mar 19, 2024)	germline	clinical testing	Citation Link,
SCV000331188	Eurofins Ntd Llc (ga)	criteria provided, single submitter (EGL Classification Definitions 2015)	Pathogenic (Nov 12, 2015)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 10477432, 8982952 Citation Link,
SCV002525841	Mayo Clinic Laboratories, Mayo Clinic	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Aug 25, 2021)	germline	clinical testing	PubMed (9) [See all records that cite these PMIDs] 10477432, 10751093, 12445909, 12809638, 15720392, 16966551, 25965562, 8982952, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000322398

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Pathogenic
(Mar 19, 2024)

germline

clinical testing

Citation Link,

SCV000331188

Eurofins Ntd Llc (ga)

criteria provided, single submitter

(EGL Classification Definitions 2015)

Pathogenic
(Nov 12, 2015)

germline

clinical testing

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

Citation Link,

SCV002525841

Mayo Clinic Laboratories, Mayo Clinic

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Aug 25, 2021)

germline

clinical testing

PubMed (9)
[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	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	4	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Identification of 12 novel mutations and two new polymorphisms in the arylsulfatase A gene: haplotype and genotype-phenotype correlation studies in Spanish metachromatic leukodystrophy patients.

Gort L, Coll MJ, Chabás A.

Hum Mutat. 1999;14(3):240-8.

PubMed [citation]

PMID:: 10477432

Characterization of four arylsulfatase A missense mutations G86D, Y201C, D255H, and E312D causing metachromatic leukodystrophy.

Hermann S, Schestag F, Polten A, Kafert S, Penzien J, Zlotogora J, Baumann N, Gieselmann V.

Am J Med Genet. 2000 Mar 6;91(1):68-73.

PubMed [citation]

PMID:: 10751093

See all PubMed Citations (9)

Details of each submission

From GeneDx, SCV000322398.7

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

Description

Published functional studies demonstrate a damaging effect: abnormal folding of protein leading to retention in endoplasmic reticulum (PMID: 15720392); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 26462614, 20301309, 25965562, 8982952, 16966551, 31589614, 12809638, 10477432, 10751093, 15720392)

#	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 Eurofins Ntd Llc (ga), SCV000331188.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	4	not provided	not provided	clinical testing	PubMed (2)

#	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		4	not provided	not provided	not provided

From Mayo Clinic Laboratories, Mayo Clinic, SCV002525841.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (9)

Description

PP3, PP4, PM2, PM3, PS3, PS4_moderate

#	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: Oct 8, 2024

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