rs104886167
Variant summary
Our verdict is Pathogenic. Variant got 16 ACMG points: 16P and 0B. PVS1PP5_Very_Strong
The NM_033380.3(COL4A5):c.2057del(p.Pro686GlnfsTer50) variant causes a frameshift change. Variant has been reported in ClinVar as Pathogenic (★★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 22)
Exomes 𝑓: 0.0 ( 0 hom. 0 hem. )
Failed GnomAD Quality Control
Consequence
COL4A5
NM_033380.3 frameshift
NM_033380.3 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 5.54
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 16 ACMG points.
PVS1
?
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PP5
?
Variant X-108601898-TC-T is Pathogenic according to our data. Variant chrX-108601898-TC-T is described in ClinVar as [Pathogenic]. Clinvar id is 24482.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-108601898-TC-T is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COL4A5 | NM_033380.3 | c.2057del | p.Pro686GlnfsTer50 | frameshift_variant | 27/53 | ENST00000328300.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL4A5 | ENST00000328300.11 | c.2057del | p.Pro686GlnfsTer50 | frameshift_variant | 27/53 | 1 | NM_033380.3 | ||
COL4A5 | ENST00000483338.1 | c.881del | p.Pro294GlnfsTer50 | frameshift_variant | 11/20 | 1 | |||
COL4A5 | ENST00000361603.7 | c.2057del | p.Pro686GlnfsTer50 | frameshift_variant | 27/51 | 2 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 22
GnomAD3 genomes
?
Cov.:
22
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1041803Hom.: 0 Cov.: 25 AF XY: 0.00 AC XY: 0AN XY: 327173
GnomAD4 exome
Data not reliable, filtered out with message: AC0
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1041803
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25
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0
AN XY:
327173
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GnomAD4 genome ? Cov.: 22
GnomAD4 genome
?
Cov.:
22
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Pathogenic:2
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | May 24, 2022 | For these reasons, this variant has been classified as Pathogenic. This sequence change creates a premature translational stop signal (p.Pro686Glnfs*50) in the COL4A5 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in COL4A5 are known to be pathogenic (PMID: 9195222, 10752524, 14514738, 24854265, 26809805). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with Alport syndrome (PMID: 17660027). ClinVar contains an entry for this variant (Variation ID: 24482). - |
Pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Oct 29, 2019 | Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 17660027, 23371956, 32812400) - |
X-linked Alport syndrome Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Feb 22, 2022 | - - |
Computational scores
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at