NM_000065.5(C6):c.226C>T (p.Gln76Ter) AND not provided

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Dec 9, 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:: RCV003851156.2

Allele description [Variation Report for NM_000065.5(C6):c.226C>T (p.Gln76Ter)]

NM_000065.5(C6):c.226C>T (p.Gln76Ter)

Gene:

C6:complement C6 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

5p13.1

Genomic location:

Preferred name:

NM_000065.5(C6):c.226C>T (p.Gln76Ter)

HGVS:

NC_000005.10:g.41201632G>A
NG_011582.1:g.64807C>T
NM_000065.5:c.226C>TMANE SELECT
NM_001115131.4:c.226C>T
NP_000056.2:p.Gln76Ter
NP_000056.2:p.Gln76Ter
NP_001108603.2:p.Gln76Ter
LRG_29t1:c.226C>T
LRG_29:g.64807C>T
LRG_29p1:p.Gln76Ter
NC_000005.9:g.41201734G>A
NM_000065.2:c.226C>T

Protein change:

Q76*

Molecular consequence:

NM_000065.5:c.226C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001115131.4:c.226C>T - nonsense - [Sequence Ontology: SO:0001587]

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
SCV004696448	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Dec 9, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 17257682, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004696448

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Dec 9, 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

Prevalence of mutations leading to complete C6 deficiency (C6Q0) in the Western Cape, South Africa and detection of novel mutations leading to C6Q0 in an Irish family.

Parham KL, Roberts A, Thomas A, Würzner R, Henderson HE, Potter PC, Morgan BP, Orren A.

Mol Immunol. 2007 Apr;44(10):2756-60. Epub 2007 Jan 25.

PubMed [citation]

PMID:: 17257682

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, SCV004696448.1

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

Description

This sequence change creates a premature translational stop signal (p.Gln76*) in the C6 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in C6 are known to be pathogenic (PMID: 17257682). This variant is present in population databases (no rsID available, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with C6-related conditions. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.

#	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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