chr11-102840234-G-A

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_002422.5(MMP3):​c.809C>T​(p.Pro270Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000105 in 1,613,630 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000068 ( 0 hom. )

Consequence

MMP3
NM_002422.5 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.360
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.07290992).
BS2
High AC in GnomAd4 at 7 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
MMP3NM_002422.5 linkuse as main transcriptc.809C>T p.Pro270Leu missense_variant 6/10 ENST00000299855.10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
MMP3ENST00000299855.10 linkuse as main transcriptc.809C>T p.Pro270Leu missense_variant 6/101 NM_002422.5 P1

Frequencies

GnomAD3 genomes
AF:
0.0000460
AC:
7
AN:
152156
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000121
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000799
AC:
2
AN:
250468
Hom.:
0
AF XY:
0.00000738
AC XY:
1
AN XY:
135426
show subpopulations
Gnomad AFR exome
AF:
0.000124
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000684
AC:
10
AN:
1461474
Hom.:
0
Cov.:
31
AF XY:
0.00000688
AC XY:
5
AN XY:
727046
show subpopulations
Gnomad4 AFR exome
AF:
0.000179
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000180
Gnomad4 OTH exome
AF:
0.0000331
GnomAD4 genome
AF:
0.0000460
AC:
7
AN:
152156
Hom.:
0
Cov.:
32
AF XY:
0.0000404
AC XY:
3
AN XY:
74332
show subpopulations
Gnomad4 AFR
AF:
0.000121
Gnomad4 AMR
AF:
0.0000655
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000332
Hom.:
0
Bravo
AF:
0.000110
ExAC
AF:
0.0000330
AC:
4

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsJan 10, 2023The c.809C>T (p.P270L) alteration is located in exon 6 (coding exon 6) of the MMP3 gene. This alteration results from a C to T substitution at nucleotide position 809, causing the proline (P) at amino acid position 270 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.077
BayesDel_addAF
Benign
-0.47
T
BayesDel_noAF
Benign
-0.67
CADD
Benign
17
DANN
Benign
0.89
DEOGEN2
Benign
0.31
T
Eigen
Benign
-0.71
Eigen_PC
Benign
-0.67
FATHMM_MKL
Benign
0.38
N
LIST_S2
Benign
0.25
T
M_CAP
Benign
0.0050
T
MetaRNN
Benign
0.073
T
MetaSVM
Benign
-0.99
T
MutationAssessor
Benign
0.0
N
MutationTaster
Benign
1.0
N
PrimateAI
Benign
0.28
T
PROVEAN
Uncertain
-2.6
D
REVEL
Benign
0.084
Sift
Benign
0.091
T
Sift4G
Benign
0.062
T
Polyphen
0.026
B
Vest4
0.11
MVP
0.52
MPC
0.022
ClinPred
0.11
T
GERP RS
4.5
Varity_R
0.16
gMVP
0.42

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs139187731; hg19: chr11-102710965; API