12-55837113-C-A

Variant names:

• chr12-55837113-C-A
• rs145965552
• NM_002429.6:c.1450G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002429.6(MMP19):​c.1450G>T​(p.Gly484Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. 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. G484R) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MMP19 NM_002429.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.392
• Publications: 4 publications found

Genes affected

MMP19 (HGNC:7165): (matrix metallopeptidase 19) This gene encodes a member of a family of proteins that 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 protein is secreted as an inactive proprotein, which is activated upon cleavage by extracellular proteases. Alternative splicing results in multiple transcript variants for this gene. [provided by RefSeq, Jan 2013]

MMP19 Gene-Disease associations (from GenCC):

• familial cavitary optic disk anomaly

  Inheritance: Unknown, AD Classification: SUPPORTIVE, LIMITED Submitted by: Laboratory for Molecular Medicine, Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17418212).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002429.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MMP19	NM_002429.6	MANE Select	c.1450G>T	p.Gly484Trp	missense	Exon 9 of 9	NP_002420.1	Q99542-1
	MMP19	NM_001414375.1		c.1204G>T	p.Gly402Trp	missense	Exon 8 of 8	NP_001401304.1
	MMP19	NM_001272101.2		c.*264G>T		3_prime_UTR	Exon 7 of 7	NP_001259030.1	Q99542-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MMP19	ENST00000322569.9	TSL:1 MANE Select	c.1450G>T	p.Gly484Trp	missense	Exon 9 of 9	ENSP00000313437.4	Q99542-1
	MMP19	ENST00000552872.5	TSL:1	n.*1335G>T		non_coding_transcript_exon	Exon 9 of 9	ENSP00000446776.1	Q99542-4
	MMP19	ENST00000552872.5	TSL:1	n.*1335G>T		3_prime_UTR	Exon 9 of 9	ENSP00000446776.1	Q99542-4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	16
DANN	Benign	0.75
DEOGEN2	Benign	0.13	T
Eigen	Benign	-0.22
Eigen_PC	Benign	-0.39
FATHMM_MKL	Benign	0.28	N
LIST_S2	Benign	0.57	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N
PhyloP100		0.39
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.073
Sift	Uncertain	0.0080	D
Sift4G	Uncertain	0.012	D
Polyphen		0.99	D
Vest4		0.30
MutPred		0.35		Gain of catalytic residue at S489 (P = 0.0012)
MVP		0.48
MPC		0.12
ClinPred		0.33	T
GERP RS		3.1
Varity_R		0.072
gMVP		0.56
Mutation Taster		=97/3	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

dbSNP: rs145965552; hg19: chr12-56230897;