rs145938503

Variant names:

• chr12-55837214-C-A
• rs145938503
• NM_002429.6:c.1349G>T

Your query was ambiguous. Multiple possible variants found:

• chr12-55837214-C-A
• chr12-55837214-C-G
• chr12-55837214-C-T

Variant summary

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

The NM_002429.6(MMP19):​c.1349G>T​(p.Arg450Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,182 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. R450C) has been classified as Uncertain significance.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: MMP19 NM_002429.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.07

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]

ACMG classification

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
MMP19	NM_002429.6	c.1349G>T	p.Arg450Leu	missense_variant	Exon 9 of 9	ENST00000322569.9	NP_002420.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MMP19	ENST00000322569.9	c.1349G>T	p.Arg450Leu	missense_variant	Exon 9 of 9	1	NM_002429.6	ENSP00000313437.4

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152182 Hom.: 0 Cov.: 32

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: 0.00316

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152182 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74342

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.31
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.24	T;.
Eigen	Benign	0.10
Eigen_PC	Benign	0.034
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.79	T;T
M_CAP	Benign	0.038	D
MetaRNN	Uncertain	0.49	T;T
MetaSVM	Benign	-1.2	T
MutationAssessor	Uncertain	2.6	M;.
PrimateAI	Benign	0.22	T
PROVEAN	Pathogenic	-6.1	D;D
REVEL	Benign	0.19
Sift	Uncertain	0.0020	D;D
Sift4G	Uncertain	0.0060	D;D
Polyphen		0.98	D;.
Vest4		0.48
MutPred		0.59		Gain of catalytic residue at W449 (P = 0.002);.;
MVP		0.53
MPC		0.42
ClinPred		0.99	D
GERP RS		3.8
Varity_R		0.50
gMVP		0.92

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

Other links and lift over

dbSNP: rs145938503; hg19: chr12-56230998;