rs1060502262
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2PP2BP4
The NM_000093.5(COL5A1):āc.2464A>Gā(p.Met822Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000662 in 151,020 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.0000066 ( 0 hom., cov: 33)
Consequence
COL5A1
NM_000093.5 missense
NM_000093.5 missense
Scores
7
12
Clinical Significance
Conservation
PhyloP100: 3.89
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 Uncertain_significance. Variant got 2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP2
?
Missense variant where missense usually causes diseases, COL5A1
BP4
?
Computational evidence support a benign effect (MetaRNN=0.39281043).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COL5A1 | NM_000093.5 | c.2464A>G | p.Met822Val | missense_variant | 29/66 | ENST00000371817.8 | |
COL5A1 | NM_001278074.1 | c.2464A>G | p.Met822Val | missense_variant | 29/66 | ||
COL5A1 | XM_017014266.3 | c.2464A>G | p.Met822Val | missense_variant | 29/65 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL5A1 | ENST00000371817.8 | c.2464A>G | p.Met822Val | missense_variant | 29/66 | 1 | NM_000093.5 | P4 | |
COL5A1 | ENST00000371820.4 | c.2464A>G | p.Met822Val | missense_variant | 29/66 | 2 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.00000662 AC: 1AN: 151020Hom.: 0 Cov.: 33
GnomAD3 genomes
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GnomAD4 exome Cov.: 32
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GnomAD4 genome ? AF: 0.00000662 AC: 1AN: 151020Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 73726
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Ehlers-Danlos syndrome, classic type, 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Nov 27, 2018 | In summary, this variant is a novel missense change with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C15"). This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a COL5A1-related disease. This sequence change replaces methionine with valine at codon 822 of the COL5A1 protein (p.Met822Val). The methionine residue is highly conserved and there is a small physicochemical difference between methionine and valine. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T
M_CAP
Uncertain
D
MetaRNN
Benign
T;T
MetaSVM
Uncertain
D
MutationAssessor
Benign
N;N
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;.
REVEL
Uncertain
Sift
Benign
T;.
Sift4G
Benign
T;T
Polyphen
B;.
Vest4
MutPred
Loss of glycosylation at K819 (P = 0.1793);Loss of glycosylation at K819 (P = 0.1793);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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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