rs1553507265
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_000090.4(COL3A1):c.608del(p.Pro203LeufsTer19) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,455,866 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 6.9e-7 ( 0 hom. )
Consequence
COL3A1
NM_000090.4 frameshift
NM_000090.4 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.496
Genes affected
COL3A1 (HGNC:2201): (collagen type III alpha 1 chain) This gene encodes the pro-alpha1 chains of type III collagen, a fibrillar collagen that is found in extensible connective tissues such as skin, lung, uterus, intestine and the vascular system, frequently in association with type I collagen. Mutations in this gene are associated with Ehlers-Danlos syndrome type IV, and with aortic and arterial aneurysms. [provided by R. Dalgleish, Feb 2008]
Genome browser will be placed here
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 2-188988610-AC-A is Pathogenic according to our data. Variant chr2-188988610-AC-A is described in ClinVar as [Pathogenic]. Clinvar id is 459794.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COL3A1 | NM_000090.4 | c.608del | p.Pro203LeufsTer19 | frameshift_variant | 7/51 | ENST00000304636.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL3A1 | ENST00000304636.9 | c.608del | p.Pro203LeufsTer19 | frameshift_variant | 7/51 | 1 | NM_000090.4 | P1 | |
COL3A1 | ENST00000450867.2 | c.608del | p.Pro203LeufsTer19 | frameshift_variant | 7/50 | 1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome AF: 6.87e-7 AC: 1AN: 1455866Hom.: 0 Cov.: 28 AF XY: 0.00000138 AC XY: 1AN XY: 724578
GnomAD4 exome
AF:
AC:
1
AN:
1455866
Hom.:
Cov.:
28
AF XY:
AC XY:
1
AN XY:
724578
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Ehlers-Danlos syndrome, type 4 Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Jan 27, 2017 | This sequence change deletes 1 nucleotide from exon 7 of the COL3A1 mRNA (c.608delC), causing a frameshift at codon 203. This creates a premature translational stop signal (p.Pro203Leufs*19) and is expected to result in an absent or disrupted protein product. While this particular variant has not been reported in the literature, loss-of-function variants in COL3A1 are known to be pathogenic (PMID: 24922459). For these reasons, this variant has been classified as Pathogenic. - |
Computational scores
Source:
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