12-14881933-T-C

Variant names:

• chr12-14881933-T-C
• rs144321187
• NM_000900.5:c.*206A>G

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_000900.5(MGP):​c.*206A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00127 in 602,182 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0037 (5 hom., cov: 32)
  • Exomes 𝑓: 0.00044 (0 hom.)
• Consequence: MGP NM_000900.5 3_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.375
• 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: Benign. The variant received -16 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 12-14881933-T-C is Benign according to our data. Variant chr12-14881933-T-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 881047.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd4 at 5 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000900.5. 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.*206A>G		3_prime_UTR	Exon 4 of 4	NP_000891.2
	MGP	NM_001190839.3		c.*206A>G		3_prime_UTR	Exon 5 of 5	NP_001177768.1	P08493-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MGP	ENST00000539261.6	TSL:1 MANE Select	c.*206A>G		3_prime_UTR	Exon 4 of 4	ENSP00000445907.1	P08493-1
	MGP	ENST00000228938.5	TSL:3	c.*206A>G		3_prime_UTR	Exon 5 of 5	ENSP00000228938.5	P08493-2
	MGP	ENST00000905127.1		c.*206A>G		3_prime_UTR	Exon 5 of 5	ENSP00000575186.1

Frequencies

GnomAD3 genomes AF: 0.00373 AC: 567 AN: 152162 Hom.: 5 Cov.: 32

Gnomad AFR AF: 0.0125

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00275

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00287

GnomAD4 exome AF: 0.000436 AC: 196 AN: 449902 Hom.: 0 Cov.: 5 AF XY: 0.000382 AC XY: 91 AN XY: 238256

African (AFR) AF: 0.0118 AC: 147 AN: 12446

American (AMR) AF: 0.00109 AC: 22 AN: 20122

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13890

East Asian (EAS) AF: 0.00 AC: 0 AN: 29440

South Asian (SAS) AF: 0.00 AC: 0 AN: 46548

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 27326

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1930

European-Non Finnish (NFE) AF: 0.0000110 AC: 3 AN: 272770

Other (OTH) AF: 0.000944 AC: 24 AN: 25430

GnomAD4 genome AF: 0.00374 AC: 570 AN: 152280 Hom.: 5 Cov.: 32 AF XY: 0.00340 AC XY: 253 AN XY: 74474

African (AFR) AF: 0.0125 AC: 520 AN: 41550

American (AMR) AF: 0.00275 AC: 42 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68028

Other (OTH) AF: 0.00284 AC: 6 AN: 2114

Alfa AF: 0.00208 Hom.: 0

Bravo AF: 0.00433

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Keutel syndrome (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.1
DANN	Benign	0.54
PhyloP100		0.38
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs144321187; hg19: chr12-15034867;