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NM_033380.3(COL4A5):c.4772del (p.His1591fs) AND X-linked Alport syndrome

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Jul 17, 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:
RCV004594814.1

Allele description [Variation Report for NM_033380.3(COL4A5):c.4772del (p.His1591fs)]

NM_033380.3(COL4A5):c.4772del (p.His1591fs)

Gene:
COL4A5:collagen type IV alpha 5 chain [Gene - OMIM - HGNC]
Variant type:
Deletion
Cytogenetic location:
Xq22.3
Genomic location:
Preferred name:
NM_033380.3(COL4A5):c.4772del (p.His1591fs)
HGVS:
  • NC_000023.11:g.108694872del
  • NG_011977.2:g.259949del
  • NM_000495.5:c.4754del
  • NM_033380.3:c.4772delMANE SELECT
  • NP_000486.1:p.His1585fs
  • NP_203699.1:p.His1591fs
  • LRG_232t1:c.4754del
  • LRG_232t2:c.4772del
  • LRG_232:g.259949del
  • LRG_232p1:p.His1585fs
  • LRG_232p2:p.His1591fs
  • NC_000023.10:g.107938102del
  • NM_033380.2:c.4772delA
Protein change:
H1585fs
Molecular consequence:
  • NM_000495.5:c.4754del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_033380.3:c.4772del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:
X-linked Alport syndrome (ATS1)
Synonyms:
NEPHROPATHY AND DEAFNESS, X-LINKED; Alport syndrome 1, X-linked recessive; Alport Syndrome and Thin Basement Membrane Nephropathy
Identifiers:
MONDO: MONDO:0010520; MedGen: C4746986; Orphanet: 63; Orphanet: 88917; OMIM: 301050

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV005086352Victorian Clinical Genetics Services, Murdoch Childrens Research Institute

See additional submitters

criteria provided, single submitter

(ACMG Guidelines, 2015)		Pathogenic
(Jul 17, 2023) 		germlineclinical testing

PubMed (5)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyesnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

COL4A3/COL4A4 mutations: from familial hematuria to autosomal-dominant or recessive Alport syndrome.

Longo I, Porcedda P, Mari F, Giachino D, Meloni I, Deplano C, Brusco A, Bosio M, Massella L, Lavoratti G, Roccatello D, Frascá G, Mazzucco G, Muda AO, Conti M, Fasciolo F, Arrondel C, Heidet L, Renieri A, De Marchi M.

Kidney Int. 2002 Jun;61(6):1947-56.

PubMed [citation]
PMID:
12028435

X-linked Alport syndrome: natural history and genotype-phenotype correlations in girls and women belonging to 195 families: a "European Community Alport Syndrome Concerted Action" study.

Jais JP, Knebelmann B, Giatras I, De Marchi M, Rizzoni G, Renieri A, Weber M, Gross O, Netzer KO, Flinter F, Pirson Y, Dahan K, Wieslander J, Persson U, Tryggvason K, Martin P, Hertz JM, Schröder C, Sanak M, Carvalho MF, Saus J, Antignac C, et al.

J Am Soc Nephrol. 2003 Oct;14(10):2603-10.

PubMed [citation]
PMID:
14514738
See all PubMed Citations (5)

Details of each submission

From Victorian Clinical Genetics Services, Murdoch Childrens Research Institute, SCV005086352.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (5)

Description

Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Pathogenic. Following criteria are met: 0103 - Dominant negative and loss of function are known mechanisms of disease in this gene and are associated with X-linked Alport syndrome 1 (MIM#301050). Dominant negative is caused mostly by glycine substitutions that affect the conformation of the protein, and loss of function can be caused by either protein truncating or missense variants (PMID: 24046192, 12028435). (I) 0110 - This gene is associated with X-linked dominant disease. Males are typically more severely affected than females (PMID: 19965530). (I) 0115 - Variants in this gene are known to have variable expressivity. There is intrafamilial variability among affected carrier females, possibly due to variable X-inactivation (PMID: 14514738). (I) 0201 - Variant is predicted to cause nonsense-mediated decay (NMD) and loss of protein (premature termination codon is located at least 54 nucleotides upstream of the final exon-exon junction). (SP) 0251 - This variant is heterozygous. (I) 0301 - Variant is absent from gnomAD (both v2 and v3). (SP) 0701 - Other NMD predicted variants comparable to the one identified in this case have very strong previous evidence for pathogenicity (DECIPHER). (SP) 0807 - This variant has no previous evidence of pathogenicity. (I) 0905 - No published segregation evidence has been identified for this variant. (I) 1007 - No published functional evidence has been identified for this variant. (I) 1208 - Inheritance information for this variant is not currently available in this individual. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign

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

Last Updated: Aug 4, 2024