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NM_000312.4(PROC):c.-54G>A AND Thrombophilia due to protein C deficiency, autosomal dominant

Germline classification:
Conflicting classifications of pathogenicity (2 submissions)
Last evaluated:
Nov 6, 2022
Review status:
criteria provided, conflicting classifications
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:
RCV001134594.13

Allele description [Variation Report for NM_000312.4(PROC):c.-54G>A]

NM_000312.4(PROC):c.-54G>A

Gene:
PROC:protein C, inactivator of coagulation factors Va and VIIIa [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
2q14.3
Genomic location:
Preferred name:
NM_000312.4(PROC):c.-54G>A
HGVS:
  • NC_000002.12:g.127418460G>A
  • NG_016323.1:g.5041G>A
  • NM_000312.4:c.-54G>AMANE SELECT
  • NM_001375602.1:c.14G>A
  • NM_001375603.1:c.14G>A
  • NM_001375604.1:c.14G>A
  • NM_001375605.1:c.-54G>A
  • NM_001375606.1:c.14G>A
  • NM_001375607.1:c.14G>A
  • NM_001375608.1:c.-54G>A
  • NM_001375609.1:c.14G>A
  • NM_001375610.1:c.-54G>A
  • NM_001375611.1:c.-70G>A
  • NP_001362531.1:p.Arg5Gln
  • NP_001362532.1:p.Arg5Gln
  • NP_001362533.1:p.Arg5Gln
  • NP_001362535.1:p.Arg5Gln
  • NP_001362536.1:p.Arg5Gln
  • NP_001362538.1:p.Arg5Gln
  • LRG_599t1:c.-54G>A
  • LRG_599:g.5041G>A
  • NC_000002.11:g.128176036G>A
  • NC_000002.11:g.128176036G>A
  • NM_000312.3:c.-54G>A
Protein change:
R5Q
Links:
dbSNP: rs2069936
NCBI 1000 Genomes Browser:
rs2069936
Molecular consequence:
  • NM_000312.4:c.-54G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001375605.1:c.-54G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001375608.1:c.-54G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001375610.1:c.-54G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001375611.1:c.-70G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001375602.1:c.14G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001375603.1:c.14G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001375604.1:c.14G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001375606.1:c.14G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001375607.1:c.14G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001375609.1:c.14G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Thrombophilia due to protein C deficiency, autosomal dominant
Synonyms:
PROC DEFICIENCY, AUTOSOMAL DOMINANT; PROTEIN C DEFICIENCY, AUTOSOMAL DOMINANT
Identifiers:
MONDO: MONDO:0008316; MedGen: C2674321; Orphanet: 745; OMIM: 176860

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001294342Illumina Laboratory Services, Illumina
criteria provided, single submitter

(ICSL Variant Classification Criteria 13 December 2019)		Uncertain significance
(Apr 27, 2017) 		germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

Citation Link,

SCV002488968Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Likely benign
(Nov 6, 2022) 		germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

A common polymorphism in the 5' region of the human protein c gene binds USF1.

Thain KR, Nakada TA, Boyd JH, Russell JA, Walley KR.

Thromb Res. 2012 Sep;130(3):451-7. doi: 10.1016/j.thromres.2012.02.045. Epub 2012 Mar 17.

PubMed [citation]
PMID:
22425321

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. doi: 10.1038/s41436-019-0624-9..

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Illumina Laboratory Services, Illumina, SCV001294342.1

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

Description

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002488968.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: May 16, 2025