11-102954362-T-G

Position:

• chr11-102954362-T-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_002427.4(MMP13):​c.512-81A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.669 in 1,600,998 control chromosomes in the GnomAD database, including 359,870 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.67 (34655 hom., cov: 33)
  • Exomes 𝑓: 0.67 (325215 hom.)
• Consequence: MMP13 NM_002427.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.42

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 11-102954362-T-G is Benign according to our data. Variant chr11-102954362-T-G is described in ClinVar as [Benign]. Clinvar id is 1277474.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.716 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MMP13	NM_002427.4	c.512-81A>C		intron_variant		ENST00000260302.8	NP_002418.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MMP13	ENST00000260302.8	c.512-81A>C		intron_variant		1	NM_002427.4	ENSP00000260302	P1
MMP13	ENST00000340273.4	c.512-81A>C		intron_variant		1		ENSP00000339672

Frequencies

GnomAD3 genomes AF: 0.672 AC: 102183 AN: 151966 Hom.: 34631 Cov.: 33

Gnomad AFR AF: 0.723

Gnomad AMI AF: 0.688

Gnomad AMR AF: 0.653

Gnomad ASJ AF: 0.591

Gnomad EAS AF: 0.468

Gnomad SAS AF: 0.595

Gnomad FIN AF: 0.604

Gnomad MID AF: 0.585

Gnomad NFE AF: 0.682

Gnomad OTH AF: 0.663

GnomAD4 exome AF: 0.668 AC: 968042 AN: 1448914 Hom.: 325215 Cov.: 29 AF XY: 0.665 AC XY: 479387 AN XY: 721126

Gnomad4 AFR exome AF: 0.731

Gnomad4 AMR exome AF: 0.656

Gnomad4 ASJ exome AF: 0.583

Gnomad4 EAS exome AF: 0.469

Gnomad4 SAS exome AF: 0.592

Gnomad4 FIN exome AF: 0.625

Gnomad4 NFE exome AF: 0.685

Gnomad4 OTH exome AF: 0.652

GnomAD4 genome AF: 0.672 AC: 102265 AN: 152084 Hom.: 34655 Cov.: 33 AF XY: 0.664 AC XY: 49322 AN XY: 74310

Gnomad4 AFR AF: 0.723

Gnomad4 AMR AF: 0.653

Gnomad4 ASJ AF: 0.591

Gnomad4 EAS AF: 0.468

Gnomad4 SAS AF: 0.595

Gnomad4 FIN AF: 0.604

Gnomad4 NFE AF: 0.682

Gnomad4 OTH AF: 0.660

Alfa AF: 0.672 Hom.: 57600

Bravo AF: 0.677

Asia WGS AF: 0.548 AC: 1909 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 12, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.20
DANN	Benign	0.64

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: rs640198; hg19: chr11-102825091;