12-14885985-A-G

Variant names:

• chr12-14885985-A-G
• rs1800802
• ENST00000527783.1:n.76-13184A>G

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The ENST00000527783.1(C12orf60):​n.76-13184A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.204 in 623,554 control chromosomes in the GnomAD database, including 14,924 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.16 (2554 hom., cov: 32)
  • Exomes 𝑓: 0.22 (12370 hom.)
• Consequence: C12orf60 ENST00000527783.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 1.49

Genes affected

C12orf60 (HGNC:28726): (chromosome 12 open reading frame 60)

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]

ACMG classification

Verdict is Benign. Variant got -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).
• BP6: Variant 12-14885985-A-G is Benign according to our data. Variant chr12-14885985-A-G is described in ClinVar as [Benign]. Clinvar id is 1166186.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.32 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MGP	NM_000900.5	c.-194T>C		upstream_gene_variant		ENST00000539261.6	NP_000891.2
MGP	NM_001190839.3	c.-194T>C		upstream_gene_variant			NP_001177768.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MGP	ENST00000539261.6	c.-194T>C		upstream_gene_variant		1	NM_000900.5	ENSP00000445907.1

Frequencies

GnomAD3 genomes AF: 0.158 AC: 23987 AN: 152132 Hom.: 2552 Cov.: 32

Gnomad AFR AF: 0.0361

Gnomad AMI AF: 0.127

Gnomad AMR AF: 0.118

Gnomad ASJ AF: 0.273

Gnomad EAS AF: 0.333

Gnomad SAS AF: 0.328

Gnomad FIN AF: 0.174

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.206

Gnomad OTH AF: 0.184

GnomAD4 exome AF: 0.219 AC: 103308 AN: 471304 Hom.: 12370 AF XY: 0.227 AC XY: 57308 AN XY: 251968

Gnomad4 AFR exome AF: 0.0378

Gnomad4 AMR exome AF: 0.0993

Gnomad4 ASJ exome AF: 0.271

Gnomad4 EAS exome AF: 0.348

Gnomad4 SAS exome AF: 0.328

Gnomad4 FIN exome AF: 0.176

Gnomad4 NFE exome AF: 0.207

Gnomad4 OTH exome AF: 0.213

GnomAD4 genome AF: 0.158 AC: 23981 AN: 152250 Hom.: 2554 Cov.: 32 AF XY: 0.158 AC XY: 11756 AN XY: 74432

Gnomad4 AFR AF: 0.0360

Gnomad4 AMR AF: 0.118

Gnomad4 ASJ AF: 0.273

Gnomad4 EAS AF: 0.333

Gnomad4 SAS AF: 0.329

Gnomad4 FIN AF: 0.174

Gnomad4 NFE AF: 0.206

Gnomad4 OTH AF: 0.181

Alfa AF: 0.189 Hom.: 1676

Bravo AF: 0.147

Asia WGS AF: 0.269 AC: 934 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Oct 16, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 11073842, 11425864) -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
CADD	Benign	16
DANN	Benign	0.88

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1800802; hg19: chr12-15038919;