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NM_000271.5(NPC1):c.3019C>G (p.Pro1007Ala) AND Inborn genetic diseases

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Jan 12, 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:
RCV002512691.3

Allele description

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]
Observations:
1

Condition(s)

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

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV003556234Ambry Genetics
criteria provided, single submitter

(Ambry General Variant Classification Scheme_2022)		Pathogenic
(Jan 12, 2021) 		germlineclinical testing

PubMed (5)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknown1not providednot provided1not providedclinical testing

Citations

PubMed

Niemann-Pick C1 disease: correlations between NPC1 mutations, levels of NPC1 protein, and phenotypes emphasize the functional significance of the putative sterol-sensing domain and of the cysteine-rich luminal loop.

Millat G, Marçais C, Tomasetto C, Chikh K, Fensom AH, Harzer K, Wenger DA, Ohno K, Vanier MT.

Am J Hum Genet. 2001 Jun;68(6):1373-85. Epub 2001 May 1.

PubMed [citation]
PMID:
11333381
PMCID:
PMC1226124

Molecular Genetics of Niemann-Pick Type C Disease in Italy: An Update on 105 Patients and Description of 18 NPC1 Novel Variants.

Dardis A, Zampieri S, Gellera C, Carrozzo R, Cattarossi S, Peruzzo P, Dariol R, Sechi A, Deodato F, Caccia C, Verrigni D, Gasperini S, Fiumara A, Fecarotta S, Carecchio M, Filosto M, Santoro L, Borroni B, Bordugo A, Brancati F, Russo CV, Di Rocco M, et al.

J Clin Med. 2020 Mar 3;9(3). doi:pii: E679. 10.3390/jcm9030679.

PubMed [citation]
PMID:
32138288
PMCID:
PMC7141276
See all PubMed Citations (5)

Details of each submission

From Ambry Genetics, SCV003556234.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testing PubMed (5)

Description

The c.3019C>G (p.P1007A) alteration is located in exon 20 (coding exon 20) of the NPC1 gene. This alteration results from a C to G substitution at nucleotide position 3019, causing the proline (P) at amino acid position 1007 to be replaced by an alanine (A). Based on data from the Genome Aggregation Database (gnomAD) database, the NPC1 c.3019C>G alteration was observed in 0.01% (33/282878) of total alleles studied, with a frequency of 0.02% (29/129196) in the European (non-Finnish) subpopulation. This mutation has been identified in numerous homozygous and compound heterozygous individuals with NPC1-related Niemann-Pick disease, many with intermediate or "variant" levels of cholesterol esterification (Millat, 2001; Jahnova, 2014; Reunert, 2016; Musalkova, 2020; Dardis, 2020). The p.P1007A alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, this alteration is classified as pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknown1not providednot provided1not providednot providednot provided

Last Updated: Apr 15, 2024