20-35226784-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_006690.4(MMP24):​c.46C>T​(p.Pro16Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0012 ( 0 hom., cov: 0)
Exomes 𝑓: 0.0000025 ( 0 hom. )

Consequence

MMP24
NM_006690.4 missense

Scores

1
2
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.925
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 Likely_benign. Variant got -4 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.018298805).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MMP24NM_006690.4 linkc.46C>T p.Pro16Ser missense_variant Exon 1 of 9 ENST00000246186.8 NP_006681.1 Q9Y5R2Q86VV6
MMP24XM_017027597.2 linkc.46C>T p.Pro16Ser missense_variant Exon 1 of 8 XP_016883086.1
MMP24XM_011528500.3 linkc.46C>T p.Pro16Ser missense_variant Exon 1 of 8 XP_011526802.1
MMP24-AS1-EDEM2NM_001355008.2 linkc.-351-8723G>A intron_variant Intron 3 of 14 NP_001341937.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MMP24ENST00000246186.8 linkc.46C>T p.Pro16Ser missense_variant Exon 1 of 9 1 NM_006690.4 ENSP00000246186.6 Q9Y5R2

Frequencies

GnomAD3 genomes
AF:
0.00116
AC:
2
AN:
1722
Hom.:
0
Cov.:
0
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00833
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:
0.00147
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.00000255
AC:
2
AN:
784660
Hom.:
0
Cov.:
15
AF XY:
0.00000551
AC XY:
2
AN XY:
362812
show subpopulations
Gnomad4 AFR exome
AF:
0.0000663
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:
0.00000139
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00116
AC:
2
AN:
1722
Hom.:
0
Cov.:
0
AF XY:
0.00113
AC XY:
1
AN XY:
884
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00833
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00147
Gnomad4 OTH
AF:
0.00

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Jan 19, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.46C>T (p.P16S) alteration is located in exon (coding exon ) of the MMP24 gene. This alteration results from a C to T substitution at nucleotide position 46, causing the proline (P) at amino acid position 16 to be replaced by a serine (S). 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
0.091
BayesDel_addAF
Benign
0.0062
T
BayesDel_noAF
Benign
-0.23
CADD
Benign
17
DANN
Benign
0.95
DEOGEN2
Benign
0.046
T
Eigen
Benign
-0.62
Eigen_PC
Benign
-0.77
FATHMM_MKL
Benign
0.0016
N
LIST_S2
Benign
0.29
T
M_CAP
Pathogenic
0.53
D
MetaRNN
Benign
0.018
T
MetaSVM
Benign
-0.47
T
MutationAssessor
Benign
0.0
N
PrimateAI
Uncertain
0.53
T
PROVEAN
Benign
0.40
N
REVEL
Uncertain
0.34
Sift
Benign
0.81
T
Sift4G
Benign
0.24
T
Polyphen
0.91
P
Vest4
0.26
MutPred
0.26
Gain of phosphorylation at P16 (P = 0.0016);
MVP
0.66
MPC
0.55
ClinPred
0.18
T
GERP RS
-0.18
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.0
Varity_R
0.041
gMVP
0.27

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: rs1254370015; hg19: chr20-33814587; API