11-102943268-T-TA

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_002427.4(MMP13):c.*997_*998insT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.16 in 151,702 control chromosomes in the GnomAD database, including 2,078 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.16 (2078 hom., cov: 29)
  • Failed GnomAD Quality Control
• Consequence: MMP13 NM_002427.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -3.40

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 -16 ACMG points.

• BP6: Variant 11-102943268-T-TA is Benign according to our data. Variant chr11-102943268-T-TA is described in ClinVar as [Benign]. Clinvar id is 301961.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.299 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MMP13	NM_002427.4	c.*997_*998insT		3_prime_UTR_variant	10/10	ENST00000260302.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MMP13	ENST00000260302.8	c.*997_*998insT		3_prime_UTR_variant	10/10	1	NM_002427.4	P1

Frequencies

GnomAD3 genomes AF: 0.160 AC: 24198 AN: 151582 Hom.: 2069 Cov.: 29

Gnomad AFR AF: 0.166

Gnomad AMI AF: 0.235

Gnomad AMR AF: 0.112

Gnomad ASJ AF: 0.176

Gnomad EAS AF: 0.234

Gnomad SAS AF: 0.311

Gnomad FIN AF: 0.0915

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.159

Gnomad OTH AF: 0.160

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: 0.160 AC: 24238 AN: 151702 Hom.: 2078 Cov.: 29 AF XY: 0.157 AC XY: 11662 AN XY: 74160

Gnomad4 AFR AF: 0.166

Gnomad4 AMR AF: 0.112

Gnomad4 ASJ AF: 0.176

Gnomad4 EAS AF: 0.234

Gnomad4 SAS AF: 0.312

Gnomad4 FIN AF: 0.0915

Gnomad4 NFE AF: 0.159

Gnomad4 OTH AF: 0.164

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Spondyloepimetaphyseal dysplasia Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 19, 2021

- -

Metaphyseal anadysplasia Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

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: rs35477433; hg19: chr11-102813997;