12-55837144-ACG-GCA

Variant names:

• chr12-55837144-ACG-GCA
• NM_002429.6:c.1417_1419delCGTinsTGC
• MMP19 p.Arg473Cys

Variant summary

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

The NM_002429.6(MMP19):​c.1417_1419delCGTinsTGC​(p.Arg473Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R473G) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MMP19 NM_002429.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.668
• Publications: 0 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.

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.1417_1419delCGTinsTGC	p.Arg473Cys	missense	N/A	NP_002420.1	Q99542-1
	MMP19	NM_001414375.1		c.1171_1173delCGTinsTGC	p.Arg391Cys	missense	N/A	NP_001401304.1
	MMP19	NM_001272101.2		c.*231_*233delCGTinsTGC		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.1417_1419delCGTinsTGC	p.Arg473Cys	missense	N/A	ENSP00000313437.4	Q99542-1
	MMP19	ENST00000552872.5	TSL:1	n.*1302_*1304delCGTinsTGC		non_coding_transcript_exon	Exon 9 of 9	ENSP00000446776.1	Q99542-4
	MMP19	ENST00000552872.5	TSL:1	n.*1302_*1304delCGTinsTGC		3_prime_UTR	Exon 9 of 9	ENSP00000446776.1	Q99542-4

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.67

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr12-56230928;