X-108440164-CTT-C
Position:
Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1PP5_Moderate
The NM_033380.3(COL4A5):c.40_41del(p.Leu14ThrfsTer25) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely pathogenic (★).
Frequency
Genomes: not found (cov: 20)
Consequence
COL4A5
NM_033380.3 frameshift
NM_033380.3 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 1.19
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 does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 102 pathogenic variants in the truncated region.
PP5
Variant X-108440164-CTT-C is Pathogenic according to our data. Variant chrX-108440164-CTT-C is described in ClinVar as [Likely_pathogenic]. Clinvar id is 1724746.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
COL4A5 | NM_033380.3 | c.40_41del | p.Leu14ThrfsTer25 | frameshift_variant | 1/53 | ENST00000328300.11 | NP_203699.1 | |
COL4A5 | NM_000495.5 | c.40_41del | p.Leu14ThrfsTer25 | frameshift_variant | 1/51 | NP_000486.1 | ||
COL4A5 | XM_047441811.1 | c.40_41del | p.Leu14ThrfsTer25 | frameshift_variant | 1/42 | XP_047297767.1 | ||
COL4A5 | XM_047441810.1 | c.-337_-336del | 5_prime_UTR_variant | 1/54 | XP_047297766.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
COL4A5 | ENST00000328300.11 | c.40_41del | p.Leu14ThrfsTer25 | frameshift_variant | 1/53 | 1 | NM_033380.3 | ENSP00000331902 |
Frequencies
GnomAD3 genomes Cov.: 20
GnomAD3 genomes
Cov.:
20
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome Cov.: 20
GnomAD4 genome
Cov.:
20
ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
X-linked Alport syndrome Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Myriad Genetics, Inc. | Feb 25, 2022 | NM_000495.4(COL4A5):c.40_41delTT(L14Tfs*25) is expected to be pathogenic in the context of X-linked Alport syndrome. This variant is predicted to lead to an abnormal or absent protein product due to the creation of a premature termination codon in COL4A5, a gene where loss-of-function variants are known to be pathogenic. Please note: this variant was assessed in the context of healthy population screening. - |
Computational scores
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Name
Calibrated prediction
Score
Prediction
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.