12-14885985-A-T

Variant names:

• chr12-14885985-A-T
• rs1800802
• ENST00000905127.1:c.-59-135T>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000905127.1(MGP):​c.-59-135T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MGP ENST00000905127.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.49
• Publications: 0 publications found

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]

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000905127.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MGP	NM_000900.5	MANE Select	c.-194T>A		upstream_gene	N/A	NP_000891.2
	MGP	NM_001190839.3		c.-194T>A		upstream_gene	N/A	NP_001177768.1	P08493-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MGP	ENST00000905127.1		c.-59-135T>A		intron	N/A	ENSP00000575186.1
	C12orf60	ENST00000527783.1	TSL:2	n.76-13184A>T		intron	N/A
	C12orf60	ENST00000533472.1	TSL:3	n.87-18022A>T		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 471822 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 252254

African (AFR) AF: 0.00 AC: 0 AN: 13002

American (AMR) AF: 0.00 AC: 0 AN: 23438

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14996

East Asian (EAS) AF: 0.00 AC: 0 AN: 30774

South Asian (SAS) AF: 0.00 AC: 0 AN: 49600

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 31182

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2044

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 280106

Other (OTH) AF: 0.00 AC: 0 AN: 26680

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	15
DANN	Benign	0.89
PhyloP100		1.5
PromoterAI		-0.19	Neutral

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;