NM_000439.5(PCSK1):c.236C>G (p.Ser79Cys) AND PCSK1-related disorder

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Aug 14, 2023
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:: RCV003414556.4

Allele description [Variation Report for NM_000439.5(PCSK1):c.236C>G (p.Ser79Cys)]

NM_000439.5(PCSK1):c.236C>G (p.Ser79Cys)

Genes:

CAST:calpastatin [Gene - OMIM - HGNC]
PCSK1:proprotein convertase subtilisin/kexin type 1 [Gene - OMIM - HGNC]
LOC101929710:uncharacterized LOC101929710 [Gene]

Variant type:

single nucleotide variant

Cytogenetic location:

5q15

Genomic location:

Preferred name:

NM_000439.5(PCSK1):c.236C>G (p.Ser79Cys)

HGVS:

NC_000005.10:g.96429262G>C
NG_021161.1:g.9020C>G
NM_000439.5:c.236C>GMANE SELECT
NM_001177875.2:c.95C>G
NM_001423250.1:c.-175+49610G>C
NM_001423251.1:c.-175+49610G>C
NM_001423252.1:c.-175+49610G>C
NM_001423253.1:c.-103+49610G>C
NM_001423254.1:c.-175+49610G>C
NM_001423255.1:c.-175+49610G>C
NM_001423256.1:c.-175+49610G>C
NM_001423257.1:c.-175+49610G>C
NM_001423258.1:c.-40+49610G>C
NM_001423259.1:c.-175+49610G>C
NM_001423260.1:c.-175+49610G>C
NP_000430.3:p.Ser79Cys
NP_001171346.1:p.Ser32Cys
NC_000005.9:g.95764966G>C
NM_000439.4:c.236C>G

Protein change:

S32C

Molecular consequence:

NM_001423250.1:c.-175+49610G>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001423251.1:c.-175+49610G>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001423252.1:c.-175+49610G>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001423253.1:c.-103+49610G>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001423254.1:c.-175+49610G>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001423255.1:c.-175+49610G>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001423256.1:c.-175+49610G>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001423257.1:c.-175+49610G>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001423258.1:c.-40+49610G>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001423259.1:c.-175+49610G>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001423260.1:c.-175+49610G>C - intron variant - [Sequence Ontology: SO:0001627]
NM_000439.5:c.236C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001177875.2:c.95C>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: PCSK1-related disorder
Synonyms:: PCSK1-related condition
Identifiers:

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004108931	PreventionGenetics, part of Exact Sciences	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Aug 14, 2023)	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

SCV004108931

PreventionGenetics, part of Exact Sciences

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Aug 14, 2023)

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

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From PreventionGenetics, part of Exact Sciences, SCV004108931.1

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

Description

The PCSK1 c.236C>G variant is predicted to result in the amino acid substitution p.Ser79Cys. This variant was observed in a cohort of obese individuals, and in vitro functional studies showed suggestive evidence of loss of function (Supplemental Data Set, Shah et al. 2023. PubMed ID: 36864747). This variant is reported in 0.011% of alleles in individuals of African descent in gnomAD (http://gnomad.broadinstitute.org/variant/5-95764966-G-C). Although we suspect that this variant may be pathogenic, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

#	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 26, 2024

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