ENST00000527783.1:n.76-13184A>G

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 60 publications found

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]

MGP Gene-Disease associations (from GenCC):

• Keutel syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000527783.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MGP	NM_000900.5	MANE Select	c.-194T>C		upstream_gene	N/A	NP_000891.2
	MGP	NM_001190839.3		c.-194T>C		upstream_gene	N/A	NP_001177768.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C12orf60	ENST00000527783.1	TSL:2	n.76-13184A>G		intron	N/A
	C12orf60	ENST00000533472.1	TSL:3	n.87-18022A>G		intron	N/A
	C12orf60	ENST00000543822.1	TSL:3	n.91+179A>G		intron	N/A

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

African (AFR) AF: 0.0378 AC: 491 AN: 13000

American (AMR) AF: 0.0993 AC: 2328 AN: 23436

Ashkenazi Jewish (ASJ) AF: 0.271 AC: 4060 AN: 14972

East Asian (EAS) AF: 0.348 AC: 10688 AN: 30714

South Asian (SAS) AF: 0.328 AC: 16257 AN: 49580

European-Finnish (FIN) AF: 0.176 AC: 5488 AN: 31130

Middle Eastern (MID) AF: 0.259 AC: 528 AN: 2040

European-Non Finnish (NFE) AF: 0.207 AC: 57797 AN: 279788

Other (OTH) AF: 0.213 AC: 5671 AN: 26644

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

African (AFR) AF: 0.0360 AC: 1498 AN: 41560

American (AMR) AF: 0.118 AC: 1808 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.273 AC: 946 AN: 3470

East Asian (EAS) AF: 0.333 AC: 1724 AN: 5176

South Asian (SAS) AF: 0.329 AC: 1586 AN: 4820

European-Finnish (FIN) AF: 0.174 AC: 1849 AN: 10600

Middle Eastern (MID) AF: 0.211 AC: 62 AN: 294

European-Non Finnish (NFE) AF: 0.206 AC: 14009 AN: 68004

Other (OTH) AF: 0.181 AC: 383 AN: 2116

Alfa AF: 0.170 Hom.: 1849

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)

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
CADD	Benign	16
DANN	Benign	0.88
PhyloP100		1.5
PromoterAI		-0.13	Neutral
Mutation Taster		=99/1	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs1800802; hg19: chr12-15038919;