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GeneBe

12-14881535-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_000900.5(MGP):c.*604A>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 0.00937 in 152,312 control chromosomes in the GnomAD database, including 32 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0094 ( 32 hom., cov: 32)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

MGP
NM_000900.5 3_prime_UTR

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.584
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]
C12orf60 (HGNC:28726): (chromosome 12 open reading frame 60)

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.91).
BP6
Variant 12-14881535-T-C is Benign according to our data. Variant chr12-14881535-T-C is described in ClinVar as [Benign]. Clinvar id is 307758.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00937 (1427/152312) while in subpopulation AFR AF= 0.032 (1332/41566). AF 95% confidence interval is 0.0306. There are 32 homozygotes in gnomad4. There are 672 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd at 27 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
MGPNM_000900.5 linkuse as main transcriptc.*604A>G 3_prime_UTR_variant 4/4 ENST00000539261.6
MGPNM_001190839.3 linkuse as main transcriptc.*604A>G 3_prime_UTR_variant 5/5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
MGPENST00000539261.6 linkuse as main transcriptc.*604A>G 3_prime_UTR_variant 4/41 NM_000900.5 P1P08493-1
C12orf60ENST00000527783.1 linkuse as main transcriptn.76-17634T>C intron_variant, non_coding_transcript_variant 2
C12orf60ENST00000533472.1 linkuse as main transcriptn.87-22472T>C intron_variant, non_coding_transcript_variant 3
C12orf60ENST00000648334.1 linkuse as main transcriptn.126-22472T>C intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes
AF:
0.00918
AC:
1397
AN:
152194
Hom.:
27
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0314
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00439
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000176
Gnomad OTH
AF:
0.00766
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1798
Hom.:
0
Cov.:
0
AF XY:
0.00
AC XY:
0
AN XY:
952
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00937
AC:
1427
AN:
152312
Hom.:
32
Cov.:
32
AF XY:
0.00902
AC XY:
672
AN XY:
74494
show subpopulations
Gnomad4 AFR
AF:
0.0320
Gnomad4 AMR
AF:
0.00439
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000176
Gnomad4 OTH
AF:
0.00758
Alfa
AF:
0.00577
Hom.:
0
Bravo
AF:
0.0103
Asia WGS
AF:
0.00549
AC:
19
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Keutel syndrome Benign:1
Benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJan 12, 2018This 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
-0.91
Cadd
Benign
4.8
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.

Other links and lift over

dbSNP: rs114512785; hg19: chr12-15034469; API