6-75102015-C-T
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Variant summary
Our verdict is Pathogenic. Variant got 13 ACMG points: 13P and 0B. PM2PP2PP3_ModeratePP5_Very_Strong
The NM_004370.6(COL12A1):c.8453G>A(p.Gly2818Glu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★★).
Frequency
Genomes: not found (cov: 32)
Consequence
COL12A1
NM_004370.6 missense
NM_004370.6 missense
Scores
13
3
1
Clinical Significance
Conservation
PhyloP100: 6.36
Genes affected
COL12A1 (HGNC:2188): (collagen type XII alpha 1 chain) This gene encodes the alpha chain of type XII collagen, a member of the FACIT (fibril-associated collagens with interrupted triple helices) collagen family. Type XII collagen is a homotrimer found in association with type I collagen, an association that is thought to modify the interactions between collagen I fibrils and the surrounding matrix. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 13 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP2
Missense variant where missense usually causes diseases, COL12A1
PP3
MetaRNN computational evidence supports a deleterious effect, 0.898
PP5
Variant 6-75102015-C-T is Pathogenic according to our data. Variant chr6-75102015-C-T is described in ClinVar as [Likely_pathogenic]. Clinvar id is 521418.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COL12A1 | NM_004370.6 | c.8453G>A | p.Gly2818Glu | missense_variant | 57/66 | ENST00000322507.13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL12A1 | ENST00000322507.13 | c.8453G>A | p.Gly2818Glu | missense_variant | 57/66 | 1 | NM_004370.6 | P4 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome Cov.: 31
GnomAD4 exome
Cov.:
31
GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Global developmental delay Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Equipe Genetique des Anomalies du Developpement, Université de Bourgogne | - | - - |
Inborn genetic diseases Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 05, 2017 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D;D;D;D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D;D;D;D;D
MetaSVM
Pathogenic
D
MutationTaster
Benign
D;D;D;N
PrimateAI
Pathogenic
D
PROVEAN
Pathogenic
D;.;D;D;D;D
REVEL
Pathogenic
Sift
Pathogenic
D;.;D;D;D;D
Sift4G
Pathogenic
D;D;D;D;D;D
Polyphen
1.0
.;.;D;D;.;.
Vest4
0.98, 0.75, 0.92, 0.72, 0.98
MutPred
0.66
.;.;Gain of solvent accessibility (P = 0.005);.;.;Gain of solvent accessibility (P = 0.005);
MVP
MPC
1.6
ClinPred
D
GERP RS
Varity_R
gMVP
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