NM_000091.5(COL4A3):c.391G>T (p.Glu131Ter) AND Alport syndrome, autosomal recessive

Clinical significance:Pathogenic/Likely pathogenic (Last evaluated: Jun 3, 2020)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000674775.2

Allele description [Variation Report for NM_000091.5(COL4A3):c.391G>T (p.Glu131Ter)]

NM_000091.5(COL4A3):c.391G>T (p.Glu131Ter)

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.391G>T (p.Glu131Ter)
HGVS:
  • NC_000002.12:g.227246688G>T
  • NG_011591.1:g.87124G>T
  • NM_000091.5:c.391G>TMANE SELECT
  • NP_000082.2:p.Glu131Ter
  • NP_000082.2:p.Glu131Ter
  • LRG_230t1:c.391G>T
  • LRG_230:g.87124G>T
  • LRG_230p1:p.Glu131Ter
  • NC_000002.11:g.228111404G>T
  • NM_000091.4:c.391G>T
Protein change:
E131*
Links:
dbSNP: rs1346138010
NCBI 1000 Genomes Browser:
rs1346138010
Molecular consequence:
  • NM_000091.5:c.391G>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:
Alport syndrome, autosomal recessive (ATS2)
Synonyms:
Alport syndrome recessive type; Nephropathy and deafness; ALPORT SYNDROME 2, AUTOSOMAL RECESSIVE; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0008762; MedGen: C4746745; Orphanet: 63; Orphanet: 88919; OMIM: 203780

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000800170Counsylcriteria provided, single submitter
Likely pathogenic
(May 23, 2018)
unknownclinical testing

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

Citation Link,

SCV001372411Women's Health and Genetics/Laboratory Corporation of America, LabCorpcriteria provided, single submitter
Pathogenic
(Jun 3, 2020)
germlineclinical testing

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

Citation Link

Summary from all submissions

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

Citations

PubMed

Structure of the human type IV collagen gene COL4A3 and mutations in autosomal Alport syndrome.

Heidet L, Arrondel C, Forestier L, Cohen-Solal L, Mollet G, Gutierrez B, Stavrou C, Gubler MC, Antignac C.

J Am Soc Nephrol. 2001 Jan;12(1):97-106. doi: 10.1681/ASN.V12197.

PubMed [citation]
PMID:
11134255

COL4A3/COL4A4 mutations and features in individuals with autosomal recessive Alport syndrome.

Storey H, Savige J, Sivakumar V, Abbs S, Flinter FA.

J Am Soc Nephrol. 2013 Dec;24(12):1945-54. doi: 10.1681/ASN.2012100985. Epub 2013 Sep 19.

PubMed [citation]
PMID:
24052634
PMCID:
PMC3839543

Details of each submission

From Counsyl, SCV000800170.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownunknownnot providednot providednot providednot providednot providednot providednot provided

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV001372411.1

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

Description

Variant summary: COL4A3 c.391G>T (p.Glu131X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant allele was found at a frequency of 8e-06 in 249198 control chromosomes (gnomAD). c.391G>T has been reported in the literature in at least one individual affected with Alport Syndrome, Autosomal Recessive (e.g. Storey_2013). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two ClinVar submitters (evaluation after 2014) cite the variant as pathogenic/likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.

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

Last Updated: Dec 4, 2021

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