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NM_033380.3(COL4A5):c.4994G>A (p.Ser1665Asn) AND not provided

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Oct 10, 2021
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:
RCV001955749.3

Allele description [Variation Report for NM_033380.3(COL4A5):c.4994G>A (p.Ser1665Asn)]

NM_033380.3(COL4A5):c.4994G>A (p.Ser1665Asn)

Gene:
COL4A5:collagen type IV alpha 5 chain [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
Xq22.3
Genomic location:
Preferred name:
NM_033380.3(COL4A5):c.4994G>A (p.Ser1665Asn)
HGVS:
  • NC_000023.11:g.108695439G>A
  • NG_011977.2:g.260516G>A
  • NM_000495.5:c.4976G>A
  • NM_033380.3:c.4994G>AMANE SELECT
  • NP_000486.1:p.Ser1659Asn
  • NP_203699.1:p.Ser1665Asn
  • LRG_232t1:c.4976G>A
  • LRG_232t2:c.4994G>A
  • LRG_232:g.260516G>A
  • LRG_232p1:p.Ser1659Asn
  • LRG_232p2:p.Ser1665Asn
  • NC_000023.10:g.107938669G>A
  • NG_011977.1:g.260516G>A
Protein change:
S1659N
Links:
dbSNP: rs104886305
NCBI 1000 Genomes Browser:
rs104886305
Molecular consequence:
  • NM_000495.5:c.4976G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_033380.3:c.4994G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:
none provided
Identifiers:
MedGen: C3661900

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002220723Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Oct 10, 2021) 		germlineclinical testing

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

Help

Summary from all submissions

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

Citations

PubMed

Aberrant 5' splice sites in human disease genes: mutation pattern, nucleotide structure and comparison of computational tools that predict their utilization.

Buratti E, Chivers M, Královicová J, Romano M, Baralle M, Krainer AR, Vorechovsky I.

Nucleic Acids Res. 2007;35(13):4250-63. Epub 2007 Jun 18.

PubMed [citation]
PMID:
17576681
PMCID:
PMC1934990

Statistical features of human exons and their flanking regions.

Zhang MQ.

Hum Mol Genet. 1998 May;7(5):919-32.

PubMed [citation]
PMID:
9536098
See all PubMed Citations (5)

Details of each submission

From Invitae, SCV002220723.3

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

Description

For these reasons, this variant has been classified as Pathogenic. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Studies have shown that this missense change results in skipping of exon 50 and introduces a new termination codon (PMID: 8940267). However the mRNA is not expected to undergo nonsense-mediated decay. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 24782). This variant is also known as 5178G>A. This missense change has been observed in individuals with clinical features of Alport syndrome (PMID: 8940267, 22921432; Invitae). This variant is not present in population databases (ExAC no frequency). This sequence change replaces serine with asparagine at codon 1659 of the COL4A5 protein (p.Ser1659Asn). The serine residue is highly conserved and there is a small physicochemical difference between serine and asparagine. RNA analysis indicates that this missense change induces altered splicing and likely disrupts the C-terminus of the protein.

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

Last Updated: Feb 14, 2024