rs476762

Variant names:

• chr11-102839976-T-A
• rs476762
• NM_002422.5:c.935+132A>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_002422.5(MMP3):​c.935+132A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.125 in 998,238 control chromosomes in the GnomAD database, including 8,944 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.11 (1258 hom., cov: 32)
  • Exomes 𝑓: 0.13 (7686 hom.)
• Consequence: MMP3 NM_002422.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.754
• Publications: 10 publications found

Genes affected

MMP3 (HGNC:7173): (matrix metallopeptidase 3) Proteins of the matrix metalloproteinase (MMP) 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. Most MMP's are secreted as inactive proproteins which are activated when cleaved by extracellular proteinases. This gene encodes an enzyme which degrades fibronectin, laminin, collagens III, IV, IX, and X, and cartilage proteoglycans. The enzyme is thought to be involved in wound repair, progression of atherosclerosis, and tumor initiation. The gene is part of a cluster of MMP genes which localize to chromosome 11q22.3. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 11-102839976-T-A is Benign according to our data. Variant chr11-102839976-T-A is described in ClinVar as Benign. ClinVar VariationId is 1286348.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.132 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MMP3	NM_002422.5	c.935+132A>T		intron_variant	Intron 6 of 9	ENST00000299855.10	NP_002413.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MMP3	ENST00000299855.10	c.935+132A>T		intron_variant	Intron 6 of 9	1	NM_002422.5	ENSP00000299855.5

Frequencies

GnomAD3 genomes AF: 0.108 AC: 16483 AN: 152058 Hom.: 1258 Cov.: 32

Gnomad AFR AF: 0.0372

Gnomad AMI AF: 0.110

Gnomad AMR AF: 0.0859

Gnomad ASJ AF: 0.126

Gnomad EAS AF: 0.0732

Gnomad SAS AF: 0.0789

Gnomad FIN AF: 0.279

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.134

Gnomad OTH AF: 0.109

GnomAD4 exome AF: 0.128 AC: 107976 AN: 846062 Hom.: 7686 AF XY: 0.126 AC XY: 53581 AN XY: 423730

African (AFR) AF: 0.0312 AC: 598 AN: 19158

American (AMR) AF: 0.0792 AC: 1407 AN: 17770

Ashkenazi Jewish (ASJ) AF: 0.135 AC: 2156 AN: 15916

East Asian (EAS) AF: 0.0993 AC: 3198 AN: 32214

South Asian (SAS) AF: 0.0831 AC: 3989 AN: 47994

European-Finnish (FIN) AF: 0.243 AC: 9647 AN: 39682

Middle Eastern (MID) AF: 0.136 AC: 376 AN: 2760

European-Non Finnish (NFE) AF: 0.130 AC: 82058 AN: 632074

Other (OTH) AF: 0.118 AC: 4547 AN: 38494

GnomAD4 genome AF: 0.108 AC: 16484 AN: 152176 Hom.: 1258 Cov.: 32 AF XY: 0.112 AC XY: 8356 AN XY: 74384

African (AFR) AF: 0.0371 AC: 1541 AN: 41544

American (AMR) AF: 0.0858 AC: 1312 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.126 AC: 438 AN: 3470

East Asian (EAS) AF: 0.0732 AC: 379 AN: 5180

South Asian (SAS) AF: 0.0794 AC: 383 AN: 4822

European-Finnish (FIN) AF: 0.279 AC: 2944 AN: 10554

Middle Eastern (MID) AF: 0.136 AC: 40 AN: 294

European-Non Finnish (NFE) AF: 0.134 AC: 9123 AN: 68002

Other (OTH) AF: 0.106 AC: 224 AN: 2112

Alfa AF: 0.126 Hom.: 184

Bravo AF: 0.0914

Asia WGS AF: 0.0690 AC: 239 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	6.3
DANN	Benign	0.51
PhyloP100		0.75
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs476762; hg19: chr11-102710707; COSMIC: COSV107351509; COSMIC: COSV107351509;