11-102943952-A-G

Variant summary

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

The NM_002427.4(MMP13):c.*314T>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 0.0374 in 274,426 control chromosomes in the GnomAD database, including 260 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.032 ( 107 hom., cov: 32)

Exomes 𝑓: 0.044 ( 153 hom. )

Consequence

MMP13
NM_002427.4 3_prime_UTR

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.696

Variant links:

Genes affected

MMP13 (HGNC:7159): (matrix metallopeptidase 13) This gene encodes a member of the peptidase M10 family of matrix metalloproteinases (MMPs). Proteins in this family are involved in the breakdown of extracellular matrix in normal physiological processes, such as embryonic development, reproduction, and tissue remodeling, as well as in disease processes, such as arthritis and metastasis. The encoded preproprotein is proteolytically processed to generate the mature protease. This protease cleaves type II collagen more efficiently than types I and III. It may be involved in articular cartilage turnover and cartilage pathophysiology associated with osteoarthritis. Mutations in this gene are associated with metaphyseal anadysplasia. This gene is part of a cluster of MMP genes on chromosome 11. [provided by RefSeq, Jan 2016]

MMP13 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BP6

Variant 11-102943952-A-G is Benign according to our data. Variant chr11-102943952-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 301970.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAdExome4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0539 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MMP13	NM_002427.4 linkuse as main transcript	c.*314T>C		3_prime_UTR_variant	10/10	ENST00000260302.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MMP13	ENST00000260302.8 linkuse as main transcript	c.*314T>C		3_prime_UTR_variant	10/10	1	NM_002427.4	P1

Frequencies

GnomAD3 genomes

AF:

0.0323

AC:

4908

AN:

152164

Hom.:

107

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00905

Gnomad AMI

AF:

0.0570

Gnomad AMR

AF:

0.0321

Gnomad ASJ

AF:

0.0807

Gnomad EAS

AF:

0.0181

Gnomad SAS

AF:

0.0553

Gnomad FIN

AF:

0.0194

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.0449

Gnomad OTH

AF:

0.0372

GnomAD4 exome

AF:

0.0439

AC:

5361

AN:

122144

Hom.:

153

Cov.:

AF XY:

0.0455

AC XY:

2953

AN XY:

64926

show subpopulations

Gnomad4 AFR exome

AF:

0.00666

Gnomad4 AMR exome

AF:

0.0269

Gnomad4 ASJ exome

AF:

0.0785

Gnomad4 EAS exome

AF:

0.0213

Gnomad4 SAS exome

AF:

0.0568

Gnomad4 FIN exome

AF:

0.0289

Gnomad4 NFE exome

AF:

0.0452

Gnomad4 OTH exome

AF:

0.0548

GnomAD4 genome

AF:

0.0322

AC:

4904

AN:

152282

Hom.:

107

Cov.:

AF XY:

0.0315

AC XY:

2344

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.00902

Gnomad4 AMR

AF:

0.0320

Gnomad4 ASJ

AF:

0.0807

Gnomad4 EAS

AF:

0.0183

Gnomad4 SAS

AF:

0.0551

Gnomad4 FIN

AF:

0.0194

Gnomad4 NFE

AF:

0.0449

Gnomad4 OTH

AF:

0.0369

Alfa

AF:

0.0384

Hom.:

Bravo

AF:

0.0320

Asia WGS

AF:

0.0400

AC:

139

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Apr 12, 2019

- -

Metaphyseal anadysplasia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 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. -

Spondyloepimetaphyseal dysplasia, Missouri type

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

Cadd

Benign

7.6

Dann

Benign

0.78

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