11-102953331-C-T

Position:

• chr11-102953331-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002427.4(MMP13):​c.637+825G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.832 in 152,138 control chromosomes in the GnomAD database, including 52,809 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.83 (52809 hom., cov: 32)
• Consequence: MMP13 NM_002427.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.948

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.873 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MMP13	NM_002427.4	c.637+825G>A		intron_variant		ENST00000260302.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MMP13	ENST00000260302.8	c.637+825G>A		intron_variant		1	NM_002427.4	P1
MMP13	ENST00000340273.4	c.637+825G>A		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.832 AC: 126504 AN: 152020 Hom.: 52782 Cov.: 32

Gnomad AFR AF: 0.803

Gnomad AMI AF: 0.764

Gnomad AMR AF: 0.885

Gnomad ASJ AF: 0.824

Gnomad EAS AF: 0.766

Gnomad SAS AF: 0.694

Gnomad FIN AF: 0.909

Gnomad MID AF: 0.905

Gnomad NFE AF: 0.842

Gnomad OTH AF: 0.833

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.832 AC: 126577 AN: 152138 Hom.: 52809 Cov.: 32 AF XY: 0.835 AC XY: 62079 AN XY: 74384

Gnomad4 AFR AF: 0.803

Gnomad4 AMR AF: 0.885

Gnomad4 ASJ AF: 0.824

Gnomad4 EAS AF: 0.766

Gnomad4 SAS AF: 0.693

Gnomad4 FIN AF: 0.909

Gnomad4 NFE AF: 0.842

Gnomad4 OTH AF: 0.830

Alfa AF: 0.844 Hom.: 6775

Bravo AF: 0.830

Asia WGS AF: 0.730 AC: 2534 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.50
DANN	Benign	0.35

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: rs655044; hg19: chr11-102824060;