Variant chr12-14885854-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000900.5(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_000900.5 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.00900

Variant links:

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]

MGP links:

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

C12orf60 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MGP	NM_000900.5 linkuse as main transcript	c.-63G>A		5_prime_UTR_variant	1/4	ENST00000539261.6	NP_000891.2
MGP	NM_001190839.3 linkuse as main transcript	c.-63G>A		5_prime_UTR_variant	1/5		NP_001177768.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MGP	ENST00000539261.6 linkuse as main transcript	c.-63G>A		5_prime_UTR_variant	1/4	1	NM_000900.5	ENSP00000445907	P1	P08493-1

Frequencies

GnomAD3 genomes

AF:

0.323

AC:

49012

AN:

151828

Hom.:

8375

Cov.:

show subpopulations

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.:

AF XY:

0.348

AC XY:

224853

AN XY:

645564

show subpopulations

Gnomad4 AFR exome

AF:

0.278

Gnomad4 AMR exome

AF:

0.340

Gnomad4 ASJ exome

AF:

0.344

Gnomad4 EAS exome

AF:

0.0890

Gnomad4 SAS exome

AF:

0.297

Gnomad4 FIN exome

AF:

0.266

Gnomad4 NFE exome

AF:

0.373

Gnomad4 OTH exome

AF:

0.333

GnomAD4 genome

AF:

0.323

AC:

49045

AN:

151946

Hom.:

8386

Cov.:

AF XY:

0.318

AC XY:

23589

AN XY:

74252

show subpopulations

Gnomad4 AFR

AF:

0.282

Gnomad4 AMR

AF:

0.350

Gnomad4 ASJ

AF:

0.352

Gnomad4 EAS

AF:

0.0878

Gnomad4 SAS

AF:

0.288

Gnomad4 FIN

AF:

0.266

Gnomad4 NFE

AF:

0.367

Gnomad4 OTH

AF:

0.327

Alfa

AF:

0.361

Hom.:

16688

Bravo

AF:

0.327

Asia WGS

AF:

0.197

AC:

687

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 08, 2018	This variant is associated with the following publications: (PMID: 24281054, 11073842) -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 15, 2024	- -

Keutel syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Mar 06, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

5.7

DANN

Benign

0.65

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over