rs1556403276
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PVS1_ModeratePM2PP5_Moderate
The ENST00000328300.11(COL4A5):c.463_465+2delAAGGT(p.Lys155del) variant causes a splice donor, conservative inframe deletion, splice region, intron change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★). Synonymous variant affecting the same amino acid position (i.e. K155K) has been classified as Uncertain significance.
Frequency
Genomes: not found (cov: 22)
Consequence
COL4A5
ENST00000328300.11 splice_donor, conservative_inframe_deletion, splice_region, intron
ENST00000328300.11 splice_donor, conservative_inframe_deletion, splice_region, intron
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 6.53
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 Likely_pathogenic. Variant got 6 ACMG points.
PVS1
Splicing +-2 bp (donor or acceptor) variant, product NOT destroyed by NMD, known LOF gene, truncates exone, which is 0.005319149 fraction of the gene. Cryptic splice site detected, with MaxEntScore 9.5, offset of -8, new splice context is: cagGTatga. Cryptic site results in frameshift change. If cryptic site found is not functional and variant results in exon loss, it results in inframe change.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant X-108571834-GAAGGT-G is Pathogenic according to our data. Variant chrX-108571834-GAAGGT-G is described in ClinVar as [Pathogenic]. Clinvar id is 447211.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
COL4A5 | ENST00000328300.11 | c.463_465+2delAAGGT | p.Lys155del | splice_donor_variant, conservative_inframe_deletion, splice_region_variant, intron_variant | Exon 8 of 53 | 1 | NM_033380.3 | ENSP00000331902.7 | ||
COL4A5 | ENST00000361603.7 | c.463_465+2delAAGGT | p.Lys155del | splice_donor_variant, conservative_inframe_deletion, splice_region_variant, intron_variant | Exon 8 of 51 | 2 | ENSP00000354505.2 |
Frequencies
GnomAD3 genomes Cov.: 22
GnomAD3 genomes
Cov.:
22
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome Cov.: 22
GnomAD4 genome
Cov.:
22
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Pathogenic:1
Oct 13, 2016
Athena Diagnostics
Significance: Pathogenic
Review Status: criteria provided, single submitter
Collection Method: clinical testing
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Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at