NM_000487.6(ARSA):c.1516G>T (p.Asp506Tyr) AND Metachromatic leukodystrophy

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Sep 1, 2022
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:: RCV002037509.3

Allele description [Variation Report for NM_000487.6(ARSA):c.1516G>T (p.Asp506Tyr)]

NM_000487.6(ARSA):c.1516G>T (p.Asp506Tyr)

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.1516G>T (p.Asp506Tyr)

HGVS:

NC_000022.11:g.50625159C>A
NG_009260.2:g.8021G>T
NM_000487.6:c.1516G>TMANE SELECT
NM_001085425.3:c.1516G>T
NM_001085426.3:c.1516G>T
NM_001085427.3:c.1516G>T
NM_001085428.3:c.1258G>T
NM_001362782.2:c.1258G>T
NP_000478.3:p.Asp506Tyr
NP_001078894.2:p.Asp506Tyr
NP_001078895.2:p.Asp506Tyr
NP_001078896.2:p.Asp506Tyr
NP_001078897.1:p.Asp420Tyr
NP_001349711.1:p.Asp420Tyr
NC_000022.10:g.51063587C>A

Protein change:

D420Y

Links:

dbSNP: rs764345345

NCBI 1000 Genomes Browser:

rs764345345

Molecular consequence:

NM_000487.6:c.1516G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001085425.3:c.1516G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001085426.3:c.1516G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001085427.3:c.1516G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001085428.3:c.1258G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001362782.2:c.1258G>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Metachromatic leukodystrophy (MLD)
Synonyms:: Metachromatic leukoencephalopathy; Sulfatide lipidosis; Cerebral sclerosis diffuse metachromatic form; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0018868; MedGen: C0023522; Orphanet: 512; OMIM: 250100

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002116043	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Sep 1, 2022)	germline	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

SCV002116043

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Sep 1, 2022)

germline

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	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002116043.2

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

Description

This sequence change replaces aspartic acid, which is acidic and polar, with tyrosine, which is neutral and polar, at codon 506 of the ARSA protein (p.Asp506Tyr). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with ARSA-related conditions. ClinVar contains an entry for this variant (Variation ID: 1345728). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#	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: Sep 29, 2024

ClinVar

Relating variation to medicine