rs1554805638
Positions:
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_000093.5(COL5A1):c.3983del(p.Pro1328LeufsTer160) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 33)
Consequence
COL5A1
NM_000093.5 frameshift
NM_000093.5 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: -0.831
Genes affected
COL5A1 (HGNC:2209): (collagen type V alpha 1 chain) This gene encodes an alpha chain for one of the low abundance fibrillar collagens. Fibrillar collagen molecules are trimers that can be composed of one or more types of alpha chains. Type V collagen is found in tissues containing type I collagen and appears to regulate the assembly of heterotypic fibers composed of both type I and type V collagen. This gene product is closely related to type XI collagen and it is possible that the collagen chains of types V and XI constitute a single collagen type with tissue-specific chain combinations. The encoded procollagen protein occurs commonly as the heterotrimer pro-alpha1(V)-pro-alpha1(V)-pro-alpha2(V). Mutations in this gene are associated with Ehlers-Danlos syndrome, types I and II. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, May 2013]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 12 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;
PP5
?
Variant 9-134814870-GC-G is Pathogenic according to our data. Variant chr9-134814870-GC-G is described in ClinVar as [Pathogenic]. Clinvar id is 519638.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COL5A1 | NM_000093.5 | c.3983del | p.Pro1328LeufsTer160 | frameshift_variant | 50/66 | ENST00000371817.8 | |
COL5A1 | NM_001278074.1 | c.3983del | p.Pro1328LeufsTer160 | frameshift_variant | 50/66 | ||
COL5A1 | XM_017014266.3 | c.3983del | p.Pro1328LeufsTer160 | frameshift_variant | 50/65 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL5A1 | ENST00000371817.8 | c.3983del | p.Pro1328LeufsTer160 | frameshift_variant | 50/66 | 1 | NM_000093.5 | P4 | |
COL5A1 | ENST00000371820.4 | c.3983del | p.Pro1328LeufsTer160 | frameshift_variant | 50/66 | 2 | A2 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
Cov.:
33
GnomAD4 exome Cov.: 31
GnomAD4 exome
Cov.:
31
GnomAD4 genome ? Cov.: 33
GnomAD4 genome
?
Cov.:
33
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Familial thoracic aortic aneurysm and aortic dissection Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 03, 2016 | The c.3983delC pathogenic mutation, located in coding exon 50 of the COL5A1 gene, results from a deletion of one nucleotide at nucleotide position 3983, causing a translational frameshift with a predicted alternate stop codon (p.P1328Lfs*160). This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. - |
Computational scores
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Calibrated prediction
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Prediction
Splicing
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Calibrated prediction
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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