Genetic Variant NM_002427.4:c.-105G>A (chr11-102955810-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

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

The NM_002427.4(MMP13):c.-105G>A variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.668 in 1,529,566 control chromosomes in the GnomAD database, including 343,519 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.67 ( 34448 hom., cov: 32)

Exomes 𝑓: 0.67 ( 309071 hom. )

Consequence

MMP13
NM_002427.4 upstream_gene

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.38

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 11-102955810-C-T is Benign according to our data. Variant chr11-102955810-C-T is described in ClinVar as [Benign]. Clinvar id is 1166185.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.71 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MMP13	NM_002427.4 link	c.-105G>A		upstream_gene_variant		ENST00000260302.8	NP_002418.1	P45452Q53H33

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MMP13	ENST00000260302.8 link	c.-105G>A		upstream_gene_variant		1	NM_002427.4	ENSP00000260302.3		P45452
MMP13	ENST00000340273.4 link	c.-105G>A		upstream_gene_variant		1		ENSP00000339672.4		G5E971

Frequencies

GnomAD3 genomes

AF:

0.671

AC:

101897

AN:

151950

Hom.:

34424

Cov.:

show subpopulations

Gnomad AFR

AF:

0.717

Gnomad AMI

AF:

0.690

Gnomad AMR

AF:

0.652

Gnomad ASJ

AF:

0.591

Gnomad EAS

AF:

0.468

Gnomad SAS

AF:

0.605

Gnomad FIN

AF:

0.604

Gnomad MID

AF:

0.585

Gnomad NFE

AF:

0.681

Gnomad OTH

AF:

0.660

GnomAD4 exome

AF:

0.668

AC:

919882

AN:

1377498

Hom.:

309071

AF XY:

0.665

AC XY:

457185

AN XY:

687902

show subpopulations

Gnomad4 AFR exome

AF:

0.724

Gnomad4 AMR exome

AF:

0.653

Gnomad4 ASJ exome

AF:

0.583

Gnomad4 EAS exome

AF:

0.469

Gnomad4 SAS exome

AF:

0.602

Gnomad4 FIN exome

AF:

0.628

Gnomad4 NFE exome

AF:

0.684

Gnomad4 OTH exome

AF:

0.652

GnomAD4 genome

AF:

0.671

AC:

101978

AN:

152068

Hom.:

34448

Cov.:

AF XY:

0.662

AC XY:

49207

AN XY:

74318

show subpopulations

Gnomad4 AFR

AF:

0.717

Gnomad4 AMR

AF:

0.652

Gnomad4 ASJ

AF:

0.591

Gnomad4 EAS

AF:

0.467

Gnomad4 SAS

AF:

0.605

Gnomad4 FIN

AF:

0.604

Gnomad4 NFE

AF:

0.681

Gnomad4 OTH

AF:

0.657

Alfa

AF:

0.681

Hom.:

3391

Bravo

AF:

0.675

Asia WGS

AF:

0.548

AC:

1907

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Oct 16, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 27245877, 26635116, 12392760, 18308831) -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

DANN

Benign

0.65

Splicing

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