NM_000487.6(ARSA):c.231_232delinsTT (p.Leu78Phe) AND Metachromatic leukodystrophy

Clinical significance:Uncertain significance (Last evaluated: Jan 22, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000791549.3

Allele description [Variation Report for NM_000487.6(ARSA):c.231_232delinsTT (p.Leu78Phe)]

NM_000487.6(ARSA):c.231_232delinsTT (p.Leu78Phe)

Gene:
ARSA:arylsulfatase A [Gene - OMIM - HGNC]
Variant type:
Indel
Cytogenetic location:
22q13.33
Genomic location:
Preferred name:
NM_000487.6(ARSA):c.231_232delinsTT (p.Leu78Phe)
HGVS:
  • NC_000022.11:g.50627399_50627400delinsAA
  • NG_009260.2:g.5780_5781delinsTT
  • NM_000487.6:c.231_232delinsTTMANE SELECT
  • NM_001085425.3:c.231_232delinsTT
  • NM_001085426.3:c.231_232delinsTT
  • NM_001085427.3:c.231_232delinsTT
  • NM_001085428.3:c.-28_-27delinsTT
  • NM_001362782.2:c.-28_-27delinsTT
  • NP_000478.3:p.Leu78Phe
  • NP_001078894.2:p.Leu78Phe
  • NP_001078895.2:p.Leu78Phe
  • NP_001078896.2:p.Leu78Phe
  • NC_000022.10:g.51065827_51065828delGGinsAA
  • NC_000022.10:g.51065827_51065828delinsAA
  • NM_000487.5:c.231_232delCCinsTT
Protein change:
L78F
Links:
dbSNP: rs1603445011
NCBI 1000 Genomes Browser:
rs1603445011
Molecular consequence:
  • NM_001085428.3:c.-28_-27delinsTT - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001362782.2:c.-28_-27delinsTT - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_000487.6:c.231_232delinsTT - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001085425.3:c.231_232delinsTT - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001085426.3:c.231_232delinsTT - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001085427.3:c.231_232delinsTT - 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

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000930804Invitaecriteria provided, single submitter
Uncertain significance
(Jan 22, 2020)
germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical 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):240-242.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Invitae, SCV000930804.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)

Description

This sequence change replaces leucine with phenylalanine at codon 78 of the ARSA protein (p.Leu78Phe). The leucine residue is highly conserved and there is a small physicochemical difference between leucine and phenylalanine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with ARSA-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: Tolerated; PolyPhen-2: Probably Damaging; Align-GVGD: Class C0). 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.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Nov 27, 2021

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