rs104886342
Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1PM2
The NM_033380.3(COL4A5):c.2062_2114dup(p.Ile706AsnfsTer48) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 23)
Consequence
COL4A5
NM_033380.3 frameshift
NM_033380.3 frameshift
Scores
Not classified
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 9.26
Genes affected
COL4A5 (HGNC:2207): (collagen type IV alpha 5 chain) This gene encodes one of the six subunits of type IV collagen, the major structural component of basement membranes. Mutations in this gene are associated with X-linked Alport syndrome, also known as hereditary nephritis. Like the other members of the type IV collagen gene family, this gene is organized in a head-to-head conformation with another type IV collagen gene so that each gene pair shares a common promoter. Alternatively spliced transcript variants have been identified for this gene. [provided by RefSeq, Aug 2010]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 10 ACMG points.
PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
COL4A5 | NM_033380.3 | c.2062_2114dup | p.Ile706AsnfsTer48 | frameshift_variant | 27/53 | ENST00000328300.11 | NP_203699.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
COL4A5 | ENST00000328300.11 | c.2062_2114dup | p.Ile706AsnfsTer48 | frameshift_variant | 27/53 | 1 | NM_033380.3 | ENSP00000331902 | ||
COL4A5 | ENST00000483338.1 | c.886_938dup | p.Ile314AsnfsTer48 | frameshift_variant | 11/20 | 1 | ENSP00000495685 | |||
COL4A5 | ENST00000361603.7 | c.2062_2114dup | p.Ile706AsnfsTer48 | frameshift_variant | 27/51 | 2 | ENSP00000354505 | P1 |
Frequencies
GnomAD3 genomes Cov.: 23
GnomAD3 genomes
Cov.:
23
GnomAD4 exome Cov.: 25
GnomAD4 exome
Cov.:
25
GnomAD4 genome Cov.: 23
GnomAD4 genome
Cov.:
23
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at