rs80337043

Variant names:

• chr12-14882112-A-C
• rs80337043
• NM_000900.5:c.*27T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BS1 BS2

The NM_000900.5(MGP):​c.*27T>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 0.00389 in 1,613,832 control chromosomes in the GnomAD database, including 150 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0032 (12 hom., cov: 31)
  • Exomes 𝑓: 0.0040 (138 hom.)
• Consequence: MGP NM_000900.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.917
• Publications: 2 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.022).
• BP6: Variant 12-14882112-A-C is Benign according to our data. Variant chr12-14882112-A-C is described in ClinVar as Benign. ClinVar VariationId is 307768.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00323 (492/152260) while in subpopulation SAS AF = 0.0423 (204/4822). AF 95% confidence interval is 0.0376. There are 12 homozygotes in GnomAd4. There are 319 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 12 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.*27T>G		3_prime_UTR	Exon 4 of 4	NP_000891.2
	MGP	NM_001190839.3		c.*27T>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.*27T>G		3_prime_UTR	Exon 4 of 4	ENSP00000445907.1	P08493-1
	MGP	ENST00000545199.5	TSL:3	c.200T>G	p.Phe67Cys	missense	Exon 2 of 2	ENSP00000445436.1	H0YGZ6
	MGP	ENST00000228938.5	TSL:3	c.*27T>G		3_prime_UTR	Exon 5 of 5	ENSP00000228938.5	P08493-2

Frequencies

GnomAD3 genomes AF: 0.00323 AC: 491 AN: 152142 Hom.: 12 Cov.: 31

Gnomad AFR AF: 0.000772

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0212

Gnomad SAS AF: 0.0419

Gnomad FIN AF: 0.0101

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000441

Gnomad OTH AF: 0.00287

GnomAD2 exomes AF: 0.00796 AC: 1999 AN: 251006 AF XY: 0.00954

Gnomad AFR exome AF: 0.00123

Gnomad AMR exome AF: 0.000202

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0225

Gnomad FIN exome AF: 0.0102

Gnomad NFE exome AF: 0.000926

Gnomad OTH exome AF: 0.00604

GnomAD4 exome AF: 0.00396 AC: 5787 AN: 1461572 Hom.: 138 Cov.: 31 AF XY: 0.00504 AC XY: 3663 AN XY: 727116

African (AFR) AF: 0.000628 AC: 21 AN: 33460

American (AMR) AF: 0.000268 AC: 12 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26124

East Asian (EAS) AF: 0.0275 AC: 1093 AN: 39686

South Asian (SAS) AF: 0.0394 AC: 3400 AN: 86244

European-Finnish (FIN) AF: 0.00992 AC: 530 AN: 53410

Middle Eastern (MID) AF: 0.00139 AC: 8 AN: 5760

European-Non Finnish (NFE) AF: 0.000353 AC: 392 AN: 1111796

Other (OTH) AF: 0.00547 AC: 330 AN: 60372

GnomAD4 genome AF: 0.00323 AC: 492 AN: 152260 Hom.: 12 Cov.: 31 AF XY: 0.00429 AC XY: 319 AN XY: 74440

African (AFR) AF: 0.000770 AC: 32 AN: 41556

American (AMR) AF: 0.000262 AC: 4 AN: 15296

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

East Asian (EAS) AF: 0.0211 AC: 109 AN: 5174

South Asian (SAS) AF: 0.0423 AC: 204 AN: 4822

European-Finnish (FIN) AF: 0.0101 AC: 107 AN: 10608

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

European-Non Finnish (NFE) AF: 0.000441 AC: 30 AN: 68012

Other (OTH) AF: 0.00284 AC: 6 AN: 2116

Alfa AF: 0.00115 Hom.: 0

Bravo AF: 0.00154

Asia WGS AF: 0.0340 AC: 120 AN: 3478

EpiCase AF: 0.000382

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: 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	-0.86
CADD	Benign	5.3
DANN	Benign	0.76
PhyloP100		0.92
Mutation Taster		=100/0	polymorphism (auto)

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: rs80337043; hg19: chr12-15035046;