NM_000271.5(NPC1):c.3019C>G (p.Pro1007Ala) AND Niemann-Pick disease, type C

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Apr 26, 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:: RCV000321958.4

Allele description [Variation Report for NM_000271.5(NPC1):c.3019C>G (p.Pro1007Ala)]

NM_000271.5(NPC1):c.3019C>G (p.Pro1007Ala)

Gene:

NPC1:NPC intracellular cholesterol transporter 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

18q11.2

Genomic location:

Preferred name:

NM_000271.5(NPC1):c.3019C>G (p.Pro1007Ala)

Other names:

p.P1007A:CCT>GCT

HGVS:

NC_000018.10:g.23538564G>C
NG_012795.1:g.53054C>G
NM_000271.5:c.3019C>GMANE SELECT
NP_000262.2:p.Pro1007Ala
NC_000018.9:g.21118528G>C
NM_000271.3:c.3019C>G
NM_000271.4:c.3019C>G
O15118:p.Pro1007Ala

Protein change:

P1007A; PRO1007ALA

Links:

UniProtKB: O15118#VAR_008834; OMIM: 607623.0012; dbSNP: rs80358257

NCBI 1000 Genomes Browser:

rs80358257

Molecular consequence:

NM_000271.5:c.3019C>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Niemann-Pick disease, type C (NPC)
Identifiers:: MONDO: MONDO:0018982; MedGen: C0220756

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000696419	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Pathogenic (Apr 26, 2017)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 10521290, 23773996, 11333381 LabCorp Variant Classification Summary - May 2015.docx Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000696419

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Pathogenic
(Apr 26, 2017)

germline

clinical testing

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

LabCorp Variant Classification Summary - May 2015.docx

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 NPC1 highlight a conserved NPC1-specific cysteine-rich domain.

Greer WL, Dobson MJ, Girouard GS, Byers DM, Riddell DC, Neumann PE.

Am J Hum Genet. 1999 Nov;65(5):1252-60.

PubMed [citation]

PMID:: 10521290
PMCID:: PMC1288277

Genetic screening for Niemann-Pick disease type C in adults with neurological and psychiatric symptoms: findings from the ZOOM study.

Bauer P, Balding DJ, Klünemann HH, Linden DE, Ory DS, Pineda M, Priller J, Sedel F, Muller A, Chadha-Boreham H, Welford RW, Strasser DS, Patterson MC.

Hum Mol Genet. 2013 Nov 1;22(21):4349-56. doi: 10.1093/hmg/ddt284. Epub 2013 Jun 16.

PubMed [citation]

PMID:: 23773996
PMCID:: PMC3792693

See all PubMed Citations (3)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000696419.1

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

Description

Variant summary: The NPC1 c.3019C>G (p.Pro1007Ala) variant involves the alteration of a highly conserved nucleotide. 4/4 in silico tools predict a damaging outcome for this variant (SNPs&GO not captured due to low reliability index). This variant was found in 14/121408 control chromosomes at a frequency of 0.0001153, which does not exceed the estimated maximal expected allele frequency of a pathogenic NPC1 variant (0.0027735). The variant has been reported numerous times in the literature in affected individuals in both the homozygous and compound heterozygous state. Multiple clinical labs classify the variant as pathogenic. Taken together, this variant 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: May 1, 2024

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