rs886038925
Positions:
Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PM1PM2PM5PP2PP3PP5_Moderate
The NM_000090.4(COL3A1):c.3500_3501delinsAA(p.Gly1167Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G1167V) has been classified as Pathogenic.
Frequency
Genomes: not found (cov: 32)
Consequence
COL3A1
NM_000090.4 missense
NM_000090.4 missense
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 10.0
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]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 10 ACMG points.
PM1
?
In a hotspot region, there are 6 aminoacids with missense pathogenic changes in the window of +-8 aminoacids around while only 0 benign, 7 uncertain in NM_000090.4
PM2
?
Very rare variant in population databases, with high coverage;
PM5
?
Other missense variant is known to change same aminoacid residue: Variant chr2-189008117-G-A is described in ClinVar as [Likely_pathogenic]. Clinvar id is 459787.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
PP2
?
Missense variant where missense usually causes diseases, COL3A1
PP3
?
No computational evidence supports a deleterious effect, but strongly conserved according to phyloP
PP5
?
Variant 2-189008117-GT-AA is Pathogenic according to our data. Variant chr2-189008117-GT-AA is described in ClinVar as [Pathogenic]. Clinvar id is 263793.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.3500_3501delinsAA | p.Gly1167Glu | missense_variant | 47/51 | ENST00000304636.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL3A1 | ENST00000304636.9 | c.3500_3501delinsAA | p.Gly1167Glu | missense_variant | 47/51 | 1 | NM_000090.4 | P1 | |
COL3A1 | ENST00000450867.2 | c.3401_3402delinsAA | p.Gly1134Glu | missense_variant | 46/50 | 1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
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
Cardiovascular phenotype Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 10, 2014 | The p.G1167E pathogenic mutation (also known as c.3500_3501delGTinsAA) is located in coding exon 47 of the COL3A1 gene. This alteration results from a deletion of GT and insertion of AA at nucleotide positions 3500-3501. The glycine at codon 1167 is replaced by glutamic acid. This amino acid position is highly conserved on sequence alignment. The majority (approximately two-thirds) of COL3A1 mutations identified to date have involved the substitution of another amino acid for glycine within the triple-helical domain (Schwarze U et al. Am J Hum Genet. 1997;61(6):1276-1286). In addition, another alteration of the same codon, p.G1167V (c.3500G>T), has been reported as pathogenic (Johnson PH et al. Hum Mutat. 1995;6(4):336-342). The p.G1167E alteration was likely the result of a de novo event in one proband tested by our laboratory; however, parental germline mosaicism cannot be ruled out. Based on the supporting evidence, p.G1167E is interpreted as a disease-causing mutation. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at