chr12-14882157-C-T
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Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 2P and 13B. PM2BP4_StrongBP6_Very_StrongBP7
The NM_000900.5(MGP):c.294G>A(p.Lys98=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000322 in 1,614,062 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 Likely benign (★★).
Frequency
Genomes: 𝑓 0.00018 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000017 ( 0 hom. )
Consequence
MGP
NM_000900.5 synonymous
NM_000900.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.583
Genes affected
MGP (HGNC:7060): (matrix Gla protein) This gene encodes a member of the osteocalcin/matrix Gla family of proteins. The encoded vitamin K-dependent protein is secreted by chondrocytes and vascular smooth muscle cells, and functions as a physiological inhibitor of ectopic tissue calcification. Carboxylation status of the encoded protein is associated with calcification of the vasculature in human patients with cardiovascular disease and calcification of the synovial membranes in osteoarthritis patients. Mutations in this gene cause Keutel syndrome in human patients, which is characterized by abnormal cartilage calcification, peripheral pulmonary stenosis and facial hypoplasia. [provided by RefSeq, Sep 2016]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -11 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.49).
BP6
Variant 12-14882157-C-T is Benign according to our data. Variant chr12-14882157-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1624298.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=0.583 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MGP | NM_000900.5 | c.294G>A | p.Lys98= | synonymous_variant | 4/4 | ENST00000539261.6 | NP_000891.2 | |
MGP | NM_001190839.3 | c.369G>A | p.Lys123= | synonymous_variant | 5/5 | NP_001177768.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MGP | ENST00000539261.6 | c.294G>A | p.Lys98= | synonymous_variant | 4/4 | 1 | NM_000900.5 | ENSP00000445907 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000177 AC: 27AN: 152132Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.0000518 AC: 13AN: 251164Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135720
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GnomAD4 exome AF: 0.0000171 AC: 25AN: 1461812Hom.: 0 Cov.: 34 AF XY: 0.0000138 AC XY: 10AN XY: 727214
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GnomAD4 genome AF: 0.000177 AC: 27AN: 152250Hom.: 0 Cov.: 31 AF XY: 0.000121 AC XY: 9AN XY: 74442
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Likely benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Apr 28, 2023 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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