NM_016042.4(EXOSC3):c.395A>C (p.Asp132Ala) AND Inborn genetic diseases

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Aug 3, 2021
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:: RCV000190687.14

Allele description [Variation Report for NM_016042.4(EXOSC3):c.395A>C (p.Asp132Ala)]

NM_016042.4(EXOSC3):c.395A>C (p.Asp132Ala)

Gene:

EXOSC3:exosome component 3 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

9p13.2

Genomic location:

Preferred name:

NM_016042.4(EXOSC3):c.395A>C (p.Asp132Ala)

HGVS:

NC_000009.12:g.37783993T>G
NG_032780.1:g.6100A>C
NM_001002269.2:c.395A>C
NM_016042.4:c.395A>CMANE SELECT
NP_001002269.1:p.Asp132Ala
NP_057126.2:p.Asp132Ala
NP_057126.2:p.Asp132Ala
NC_000009.11:g.37783990T>G
NM_016042.2:c.395A>C
NM_016042.3:c.395A>C
Q9NQT5:p.Asp132Ala

Protein change:

D132A; ASP132ALA

Links:

UniProtKB: Q9NQT5#VAR_068506; OMIM: 606489.0001; dbSNP: rs141138948

NCBI 1000 Genomes Browser:

rs141138948

Molecular consequence:

NM_001002269.2:c.395A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_016042.4:c.395A>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Inborn genetic diseases
Identifiers:: MeSH: D030342; MedGen: C0950123

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
SCV000244128	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Pathogenic (Aug 3, 2021)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 22544365, 23564332, 24524299 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000244128

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Pathogenic
(Aug 3, 2021)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

Citation Link

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

Mutations in the RNA exosome component gene EXOSC3 cause pontocerebellar hypoplasia and spinal motor neuron degeneration.

Wan J, Yourshaw M, Mamsa H, Rudnik-Schöneborn S, Menezes MP, Hong JE, Leong DW, Senderek J, Salman MS, Chitayat D, Seeman P, von Moers A, Graul-Neumann L, Kornberg AJ, Castro-Gago M, Sobrido MJ, Sanefuji M, Shieh PB, Salamon N, Kim RC, Vinters HV, Chen Z, et al.

Nat Genet. 2012 Apr 29;44(6):704-8. doi: 10.1038/ng.2254.

PubMed [citation]

PMID:: 22544365
PMCID:: PMC3366034

EXOSC3 mutations in isolated cerebellar hypoplasia and spinal anterior horn involvement.

Biancheri R, Cassandrini D, Pinto F, Trovato R, Di Rocco M, Mirabelli-Badenier M, Pedemonte M, Panicucci C, Trucks H, Sander T, Zara F, Rossi A, Striano P, Minetti C, Santorelli FM.

J Neurol. 2013 Jul;260(7):1866-70. doi: 10.1007/s00415-013-6896-0. Epub 2013 Apr 7.

PubMed [citation]

PMID:: 23564332

See all PubMed Citations (3)

Details of each submission

From Ambry Genetics, SCV000244128.9

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

The c.395A>C (p.D132A) alteration is located in exon 2 (coding exon 2) of the EXOSC3 gene. This alteration results from an A to C substitution at nucleotide position 395, causing the aspartic acid (D) at amino acid position 132 to be replaced by an alanine (A). Based on data from the Genome Aggregation Database (gnomAD), the EXOSC3 c.395A>C alteration was observed in 0.04% (115/282766) of total alleles studied, with a frequency of 0.07% (94/129130) in the European (non-Finnish) subpopulation. The c.395A>C (p.D132A) alteration is the most common cause of EXOSC3-related pontocerebellar hypoplasia. This mutation has been reported in multiple affected individuals in the homozygous or compound heterozygous state (Wan, 2012; Biancheri, 2013; Eggens, 2014). The p.D132A alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, this alteration is classified as pathogenic.

#	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 13, 2024

ClinVar

Relating variation to medicine