NM_000091.5(COL4A3):c.4546C>T (p.Arg1516Ter) AND not provided

Germline classification:: Pathogenic (1 submission)
Last evaluated:: May 23, 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:: RCV001066963.9

Allele description [Variation Report for NM_000091.5(COL4A3):c.4546C>T (p.Arg1516Ter)]

NM_000091.5(COL4A3):c.4546C>T (p.Arg1516Ter)

Genes:

MFF-DT:MFF divergent transcript [Gene - HGNC]
COL4A3:collagen type IV alpha 3 chain [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

2q36.3

Genomic location:

Preferred name:

NM_000091.5(COL4A3):c.4546C>T (p.Arg1516Ter)

HGVS:

NC_000002.12:g.227308982C>T
NG_011591.1:g.149418C>T
NM_000091.5:c.4546C>TMANE SELECT
NP_000082.2:p.Arg1516Ter
NP_000082.2:p.Arg1516Ter
LRG_230t1:c.4546C>T
LRG_230:g.149418C>T
LRG_230p1:p.Arg1516Ter
NC_000002.11:g.228173698C>T
NM_000091.4:c.4546C>T

Protein change:

R1516*

Links:

dbSNP: rs759873621

NCBI 1000 Genomes Browser:

rs759873621

Molecular consequence:

NM_000091.5:c.4546C>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
SCV001231989	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (May 23, 2023)	germline	clinical testing	PubMed (8) [See all records that cite these PMIDs] 15954103, 18436078, 30881523, 8956999, 24854265, 26809805, 27281700, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001231989

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(May 23, 2023)

germline

clinical testing

PubMed (8)
[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

Novel COL4A5, COL4A4, and COL4A3 mutations in Alport syndrome.

Nagel M, Nagorka S, Gross O.

Hum Mutat. 2005 Jul;26(1):60.

PubMed [citation]

PMID:: 15954103

Novel COL4A3 mutations in African American siblings with autosomal recessive Alport syndrome.

Cook C, Friedrich CA, Baliga R.

Am J Kidney Dis. 2008 May;51(5):e25-8. doi: 10.1053/j.ajkd.2007.09.028. Epub 2008 Apr 2.

PubMed [citation]

PMID:: 18436078

See all PubMed Citations (8)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001231989.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (8)

Description

This premature translational stop signal has been observed in individual(s) with autosomal recessive Alport syndrome (PMID: 15954103, 18436078, 30881523). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. This sequence change creates a premature translational stop signal (p.Arg1516*) in the COL4A3 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in COL4A3 are known to be pathogenic (PMID: 8956999, 24854265, 26809805, 27281700). This variant is present in population databases (rs759873621, gnomAD 0.0009%). ClinVar contains an entry for this variant (Variation ID: 552261). 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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