rs148802642

Variant names:

• chr12-14881999-A-G
• rs148802642
• NM_000900.5:c.*140T>C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_000900.5(MGP):​c.*140T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000681 in 1,072,520 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0030 (3 hom., cov: 32)
  • Exomes 𝑓: 0.00030 (1 hom.)
• Consequence: MGP NM_000900.5 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.23
• 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 12-14881999-A-G is Benign according to our data. Variant chr12-14881999-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 307767.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 3 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.*140T>C		3_prime_UTR	Exon 4 of 4	NP_000891.2
	MGP	NM_001190839.3		c.*140T>C		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.*140T>C		3_prime_UTR	Exon 4 of 4	ENSP00000445907.1	P08493-1
	MGP	ENST00000228938.5	TSL:3	c.*140T>C		3_prime_UTR	Exon 5 of 5	ENSP00000228938.5	P08493-2
	MGP	ENST00000905127.1		c.*140T>C		3_prime_UTR	Exon 5 of 5	ENSP00000575186.1

Frequencies

GnomAD3 genomes AF: 0.00302 AC: 459 AN: 152114 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.0106

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000655

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: 0.0000147

Gnomad OTH AF: 0.00335

GnomAD4 exome AF: 0.000296 AC: 272 AN: 920288 Hom.: 1 Cov.: 12 AF XY: 0.000241 AC XY: 114 AN XY: 472936

African (AFR) AF: 0.00984 AC: 218 AN: 22154

American (AMR) AF: 0.000557 AC: 20 AN: 35888

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21492

East Asian (EAS) AF: 0.00 AC: 0 AN: 35268

South Asian (SAS) AF: 0.00 AC: 0 AN: 70164

European-Finnish (FIN) AF: 0.0000248 AC: 1 AN: 40322

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3278

European-Non Finnish (NFE) AF: 0.0000292 AC: 19 AN: 649656

Other (OTH) AF: 0.000333 AC: 14 AN: 42066

GnomAD4 genome AF: 0.00301 AC: 458 AN: 152232 Hom.: 3 Cov.: 32 AF XY: 0.00287 AC XY: 214 AN XY: 74442

African (AFR) AF: 0.0106 AC: 440 AN: 41538

American (AMR) AF: 0.000654 AC: 10 AN: 15280

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

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

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68014

Other (OTH) AF: 0.00331 AC: 7 AN: 2114

Alfa AF: 0.00187 Hom.: 0

Bravo AF: 0.00320

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Keutel syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	3.8
DANN	Benign	0.82
PhyloP100		2.2
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: rs148802642; hg19: chr12-15034933;