NM_006690.4:c.362C>A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_006690.4(MMP24):​c.362C>A​(p.Pro121Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,710 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P121L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

MMP24
NM_006690.4 missense

Scores

7
12

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.14
Variant links:
Genes affected
MMP24 (HGNC:7172): (matrix metallopeptidase 24) 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. Unlike most MMPs, which are secreted, this protease is a member of the membrane-type MMP (MT-MMP) subfamily, contains a transmembrane domain and is expressed at the cell surface. Substrates of this protease include the proteins cadherin 2 and matrix metallopeptidase 2 (also known as 72 kDa type IV collagenase). The gene has previously been referred to as MMP25 but has been renamed matrix metallopeptidase 24 (MMP24). [provided by RefSeq, Oct 2019]
MMP24OS (HGNC:44421): (MMP24 opposite strand)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MMP24NM_006690.4 linkc.362C>A p.Pro121Gln missense_variant Exon 2 of 9 ENST00000246186.8 NP_006681.1 Q9Y5R2Q86VV6

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MMP24ENST00000246186.8 linkc.362C>A p.Pro121Gln missense_variant Exon 2 of 9 1 NM_006690.4 ENSP00000246186.6 Q9Y5R2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000342
AC:
5
AN:
1461710
Hom.:
0
Cov.:
32
AF XY:
0.00000413
AC XY:
3
AN XY:
727138
show subpopulations
Gnomad4 AFR exome
AF:
0.00
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:
0.00000450
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.12
BayesDel_addAF
Uncertain
0.013
T
BayesDel_noAF
Benign
-0.22
CADD
Benign
23
DANN
Uncertain
0.99
DEOGEN2
Benign
0.11
T
Eigen
Benign
0.13
Eigen_PC
Uncertain
0.28
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Benign
0.86
D
M_CAP
Benign
0.019
T
MetaRNN
Uncertain
0.46
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Uncertain
2.2
M
PrimateAI
Uncertain
0.77
T
PROVEAN
Benign
-1.2
N
REVEL
Benign
0.11
Sift
Benign
0.32
T
Sift4G
Benign
0.62
T
Polyphen
0.28
B
Vest4
0.62
MutPred
0.48
Gain of catalytic residue at P121 (P = 0.1285);
MVP
0.71
MPC
1.4
ClinPred
0.92
D
GERP RS
5.5
Varity_R
0.16
gMVP
0.71

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr20-33834758; API