chr12-14885854-C-T

Variant names:

• chr12-14885854-C-T
• rs1800801
• NM_000900.5:c.-63G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001190839.3(MGP):​c.-63G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.346 in 1,431,672 control chromosomes in the GnomAD database, including 89,490 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.32 (8386 hom., cov: 32)
  • Exomes 𝑓: 0.35 (81104 hom.)
• Consequence: MGP NM_001190839.3 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.00900
• Publications: 72 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 12-14885854-C-T is Benign according to our data. Variant chr12-14885854-C-T is described in ClinVar as Benign. ClinVar VariationId is 307776.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.363 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001190839.3. 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.-63G>A		5_prime_UTR	Exon 1 of 4	NP_000891.2
	MGP	NM_001190839.3		c.-63G>A		5_prime_UTR	Exon 1 of 5	NP_001177768.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MGP	ENST00000539261.6	TSL:1 MANE Select	c.-63G>A		5_prime_UTR	Exon 1 of 4	ENSP00000445907.1
	MGP	ENST00000507170.2	TSL:1	n.1G>A		non_coding_transcript_exon	Exon 1 of 2
	MGP	ENST00000228938.5	TSL:3	c.-63G>A		5_prime_UTR	Exon 1 of 5	ENSP00000228938.5

Frequencies

GnomAD3 genomes AF: 0.323 AC: 49012 AN: 151828 Hom.: 8375 Cov.: 32

Gnomad AFR AF: 0.282

Gnomad AMI AF: 0.511

Gnomad AMR AF: 0.350

Gnomad ASJ AF: 0.352

Gnomad EAS AF: 0.0880

Gnomad SAS AF: 0.287

Gnomad FIN AF: 0.266

Gnomad MID AF: 0.361

Gnomad NFE AF: 0.367

Gnomad OTH AF: 0.326

GnomAD4 exome AF: 0.349 AC: 446929 AN: 1279726 Hom.: 81104 Cov.: 18 AF XY: 0.348 AC XY: 224853 AN XY: 645564

African (AFR) AF: 0.278 AC: 8279 AN: 29800

American (AMR) AF: 0.340 AC: 14870 AN: 43758

Ashkenazi Jewish (ASJ) AF: 0.344 AC: 8572 AN: 24952

East Asian (EAS) AF: 0.0890 AC: 3453 AN: 38806

South Asian (SAS) AF: 0.297 AC: 24317 AN: 81774

European-Finnish (FIN) AF: 0.266 AC: 14062 AN: 52896

Middle Eastern (MID) AF: 0.377 AC: 1981 AN: 5258

European-Non Finnish (NFE) AF: 0.373 AC: 353195 AN: 947906

Other (OTH) AF: 0.333 AC: 18200 AN: 54576

GnomAD4 genome AF: 0.323 AC: 49045 AN: 151946 Hom.: 8386 Cov.: 32 AF XY: 0.318 AC XY: 23589 AN XY: 74252

African (AFR) AF: 0.282 AC: 11666 AN: 41416

American (AMR) AF: 0.350 AC: 5343 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.352 AC: 1219 AN: 3466

East Asian (EAS) AF: 0.0878 AC: 454 AN: 5168

South Asian (SAS) AF: 0.288 AC: 1384 AN: 4806

European-Finnish (FIN) AF: 0.266 AC: 2806 AN: 10564

Middle Eastern (MID) AF: 0.364 AC: 107 AN: 294

European-Non Finnish (NFE) AF: 0.367 AC: 24915 AN: 67956

Other (OTH) AF: 0.327 AC: 687 AN: 2104

Alfa AF: 0.355 Hom.: 26354

Bravo AF: 0.327

Asia WGS AF: 0.197 AC: 687 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	Keutel syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	5.7
DANN	Benign	0.65
PhyloP100		-0.0090
PromoterAI		-0.19	Neutral
Mutation Taster		=300/0	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: rs1800801; hg19: chr12-15038788; COSMIC: COSV57454325; COSMIC: COSV57454325;