chr20-35226779-C-A

Variant names:

• chr20-35226779-C-A
• NM_006690.4:c.41C>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_006690.4(MMP24):​c.41C>A​(p.Pro14Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MMP24 NM_006690.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0720
• Publications: 0 publications found

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]

MMP24-AS1-EDEM2 (HGNC:):

MMP24OS (HGNC:44421): (MMP24 opposite strand)

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.063458204).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MMP24	NM_006690.4	c.41C>A	p.Pro14Gln	missense_variant	Exon 1 of 9	ENST00000246186.8	NP_006681.1
MMP24	XM_017027597.2	c.41C>A	p.Pro14Gln	missense_variant	Exon 1 of 8		XP_016883086.1
MMP24	XM_011528500.3	c.41C>A	p.Pro14Gln	missense_variant	Exon 1 of 8		XP_011526802.1
MMP24-AS1-EDEM2	NM_001355008.2	c.-351-8718G>T		intron_variant	Intron 3 of 14		NP_001341937.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MMP24	ENST00000246186.8	c.41C>A	p.Pro14Gln	missense_variant	Exon 1 of 9	1	NM_006690.4	ENSP00000246186.6

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 53854 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 154482 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 71486

African (AFR) AF: 0.00 AC: 0 AN: 12828

American (AMR) AF: 0.00 AC: 0 AN: 114

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1476

East Asian (EAS) AF: 0.00 AC: 0 AN: 428

South Asian (SAS) AF: 0.00 AC: 0 AN: 6122

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 58

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 480

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 127510

Other (OTH) AF: 0.00 AC: 0 AN: 5466

GnomAD4 genome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 53854 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 26052

African (AFR) AF: 0.00 AC: 0 AN: 32204

American (AMR) AF: 0.00 AC: 0 AN: 2752

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 976

East Asian (EAS) AF: 0.00 AC: 0 AN: 570

South Asian (SAS) AF: 0.00 AC: 0 AN: 1758

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 1938

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 84

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 12738

Other (OTH) AF: 0.00 AC: 0 AN: 594

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Apr 07, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.41C>A (p.P14Q) alteration is located in exon (coding exon ) of the MMP24 gene. This alteration results from a C to A substitution at nucleotide position 41, causing the proline (P) at amino acid position 14 to be replaced by a glutamine (Q). 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	0.11
BayesDel_addAF	Uncertain	0.015	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	15
DANN	Benign	0.90
DEOGEN2	Benign	0.048	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.0019	N
LIST_S2	Benign	0.28	T
M_CAP	Uncertain	0.086	D
MetaRNN	Benign	0.063	T
MetaSVM	Benign	-0.82	T
MutationAssessor	Benign	0.0	N
PhyloP100		-0.072
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-0.13	N
REVEL	Benign	0.24
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.16	B
Vest4		0.28
MutPred		0.23		Loss of glycosylation at P14 (P = 4e-04);
MVP		0.47
MPC		0.50
ClinPred		0.16	T
GERP RS		-2.9
PromoterAI		0.021	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.10
gMVP		0.25
Mutation Taster		=96/4	polymorphism

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

hg19: chr20-33814582;