NM_005051.3(QARS1):c.858C>A (p.Phe286Leu) AND Diffuse cerebral and cerebellar atrophy - intractable seizures - progressive microcephaly syndrome - ClinVar

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NM_005051.3(QARS1):c.858C>A (p.Phe286Leu) AND Diffuse cerebral and cerebellar atrophy - intractable seizures - progressive microcephaly syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: May 16, 2017
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:: RCV000533941.1

Allele description

NM_005051.3(QARS1):c.858C>A (p.Phe286Leu)

Gene:

QARS1:glutaminyl-tRNA synthetase 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

3p21.31

Genomic location:

Preferred name:

NM_005051.3(QARS1):c.858C>A (p.Phe286Leu)

HGVS:

NC_000003.12:g.49101373G>T
NG_042312.1:g.8757C>A
NM_001272073.2:c.825C>A
NM_005051.3:c.858C>AMANE SELECT
NP_001259002.1:p.Phe275Leu
NP_005042.1:p.Phe286Leu
NC_000003.11:g.49138806G>T
NM_005051.2:c.858C>A
NR_073590.2:n.833C>A
p.Phe286Leu

Protein change:

F275L

Links:

dbSNP: rs1307590384

NCBI 1000 Genomes Browser:

rs1307590384

Molecular consequence:

NM_001272073.2:c.825C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_005051.3:c.858C>A - missense variant - [Sequence Ontology: SO:0001583]
NR_073590.2:n.833C>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Diffuse cerebral and cerebellar atrophy - intractable seizures - progressive microcephaly syndrome
Synonyms:: Microcephaly, progressive, with seizures and cerebral and cerebellar atrophy
Identifiers:: MONDO: MONDO:0014335; MedGen: C4014239; Orphanet: 404437; OMIM: 615760

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000659336	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (May 16, 2017)	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

SCV000659336

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(May 16, 2017)

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):240-242.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Invitae, SCV000659336.1

#	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 phenylalanine with leucine at codon 286 of the QARS protein (p.Phe286Leu). The phenylalanine residue is moderately conserved and there is a small physicochemical difference between phenylalanine and leucine. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a QARS-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, this variant is a novel missense change with uncertain impact on protein function. 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: Apr 1, 2023

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