NM_000064.4(C3):c.1402G>A (p.Gly468Arg) AND Atypical hemolytic-uremic syndrome with C3 anomaly

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Mar 30, 2021
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV001353350.5

Allele description [Variation Report for NM_000064.4(C3):c.1402G>A (p.Gly468Arg)]

NM_000064.4(C3):c.1402G>A (p.Gly468Arg)

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.1402G>A (p.Gly468Arg)

HGVS:

NC_000019.10:g.6711064C>T
NG_009557.1:g.14588G>A
NM_000064.4:c.1402G>AMANE SELECT
NP_000055.2:p.Gly468Arg
LRG_27:g.14588G>A
NC_000019.9:g.6711075C>T
NM_000064.3:c.1402G>A

Protein change:

G468R

Links:

dbSNP: rs148820222

NCBI 1000 Genomes Browser:

rs148820222

Molecular consequence:

NM_000064.4:c.1402G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Atypical hemolytic-uremic syndrome with C3 anomaly
Synonyms:: AHUS, SUSCEPTIBILITY TO, 5; Atypical hemolytic-uremic syndrome 5
Identifiers:: MONDO: MONDO:0013043; MedGen: C2752037; Orphanet: 2134; OMIM: 612925

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001548500	Johns Hopkins Genomics, Johns Hopkins University	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Mar 30, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV001984001	Al Jalila Children’s Genomics Center, Al Jalila Childrens Speciality Hospital	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Apr 28, 2020)	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

SCV001548500

Johns Hopkins Genomics, Johns Hopkins University

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Mar 30, 2021)

germline

clinical testing

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

SCV001984001

Al Jalila Children’s Genomics Center, Al Jalila Childrens Speciality Hospital

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Apr 28, 2020)

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	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
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 Johns Hopkins Genomics, Johns Hopkins University, SCV001548500.1

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

Description

C3 c.1402G>A (rs148820222) is rare (<0.1%) in a large population dataset (gnomAD: 2/282848 total alleles; 0.0007%; no homozygotes) and has not been reported in ClinVar nor the literature, to our knowledge. Three bioinformatic tools queried predict that this substitution would be damaging and the glycine residue at this position is evolutionarily conserved across most species assessed. We consider the clinical significance of C3 c.1402G>A to be uncertain at this time.

#	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

From Al Jalila Children’s Genomics Center, Al Jalila Childrens Speciality Hospital, SCV001984001.1

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

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Feb 25, 2025

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