NM_000064.4(C3):c.640C>T (p.Pro214Ser) AND not provided

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Aug 4, 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:: RCV003727628.2

Allele description [Variation Report for NM_000064.4(C3):c.640C>T (p.Pro214Ser)]

NM_000064.4(C3):c.640C>T (p.Pro214Ser)

Gene:

C3:complement C3 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

19p13.3

Genomic location:

Preferred name:

NM_000064.4(C3):c.640C>T (p.Pro214Ser)

HGVS:

NC_000019.10:g.6714208G>A
NG_009557.1:g.11444C>T
NM_000064.4:c.640C>TMANE SELECT
NP_000055.2:p.Pro214Ser
LRG_27:g.11444C>T
NC_000019.9:g.6714219G>A

Protein change:

P214S

Links:

dbSNP: rs794729228

NCBI 1000 Genomes Browser:

rs794729228

Molecular consequence:

NM_000064.4:c.640C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004539064	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Aug 4, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 29888403, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004539064

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Aug 4, 2023)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

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

Genotype-phenotype correlations of low-frequency variants in the complement system in renal disease and age-related macular degeneration.

Geerlings MJ, Volokhina EB, de Jong EK, van de Kar N, Pauper M, Hoyng CB, van den Heuvel LP, den Hollander AI.

Clin Genet. 2018 Oct;94(3-4):330-338. doi: 10.1111/cge.13392. Epub 2018 Jul 10.

PubMed [citation]

PMID:: 29888403
PMCID:: PMC6175426

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 Labcorp Genetics (formerly Invitae), Labcorp, SCV004539064.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt C3 protein function. ClinVar contains an entry for this variant (Variation ID: 202203). This missense change has been observed in individual(s) with C3-related conditions (PMID: 29888403). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 214 of the C3 protein (p.Pro214Ser).

#	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: Sep 29, 2024

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