11-102943381-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_002427.4(MMP13):c.*885A>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 0.261 in 152,090 control chromosomes in the GnomAD database, including 5,567 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.26 (5567 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: MMP13 NM_002427.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 0.469

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 11-102943381-T-C is Benign according to our data. Variant chr11-102943381-T-C is described in ClinVar as [Benign]. Clinvar id is 301962.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.401 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MMP13	NM_002427.4	c.*885A>G		3_prime_UTR_variant	10/10	ENST00000260302.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MMP13	ENST00000260302.8	c.*885A>G		3_prime_UTR_variant	10/10	1	NM_002427.4	P1

Frequencies

GnomAD3 genomes AF: 0.261 AC: 39737 AN: 151972 Hom.: 5568 Cov.: 32

Gnomad AFR AF: 0.169

Gnomad AMI AF: 0.252

Gnomad AMR AF: 0.300

Gnomad ASJ AF: 0.321

Gnomad EAS AF: 0.416

Gnomad SAS AF: 0.315

Gnomad FIN AF: 0.376

Gnomad MID AF: 0.380

Gnomad NFE AF: 0.272

Gnomad OTH AF: 0.269

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.261 AC: 39747 AN: 152090 Hom.: 5567 Cov.: 32 AF XY: 0.272 AC XY: 20210 AN XY: 74324

Gnomad4 AFR AF: 0.169

Gnomad4 AMR AF: 0.300

Gnomad4 ASJ AF: 0.321

Gnomad4 EAS AF: 0.416

Gnomad4 SAS AF: 0.315

Gnomad4 FIN AF: 0.376

Gnomad4 NFE AF: 0.272

Gnomad4 OTH AF: 0.267

Alfa AF: 0.217 Hom.: 1053

Bravo AF: 0.254

Asia WGS AF: 0.336 AC: 1169 AN: 3474

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

Submissions by phenotype

Metaphyseal anadysplasia Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 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 12, 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	-0.82
Cadd	Benign	6.1
Dann	Benign	0.87

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

Other links and lift over

dbSNP: rs1042840; hg19: chr11-102814110;