chr12-55837196-C-T

Variant names:

• chr12-55837196-C-T
• rs150724096
• NM_002429.6:c.1367G>A

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_002429.6(MMP19):​c.1367G>A​(p.Arg456Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00507 in 1,614,180 control chromosomes in the GnomAD database, including 28 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0035 (3 hom., cov: 32)
  • Exomes 𝑓: 0.0052 (25 hom.)
• Consequence: MMP19 NM_002429.6 missense
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.0580
• Publications: 13 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: Benign. The variant received -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0056241155).
• BP6: Variant 12-55837196-C-T is Benign according to our data. Variant chr12-55837196-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 773261.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd4 at 537 Unknown,AD gene.

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.1367G>A	p.Arg456Gln	missense	Exon 9 of 9	NP_002420.1	Q99542-1
	MMP19	NM_001414375.1		c.1121G>A	p.Arg374Gln	missense	Exon 8 of 8	NP_001401304.1
	MMP19	NM_001272101.2		c.*181G>A		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.1367G>A	p.Arg456Gln	missense	Exon 9 of 9	ENSP00000313437.4	Q99542-1
	MMP19	ENST00000552872.5	TSL:1	n.*1252G>A		non_coding_transcript_exon	Exon 9 of 9	ENSP00000446776.1	Q99542-4
	MMP19	ENST00000552872.5	TSL:1	n.*1252G>A		3_prime_UTR	Exon 9 of 9	ENSP00000446776.1	Q99542-4

Frequencies

GnomAD3 genomes AF: 0.00352 AC: 536 AN: 152188 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.00130

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00523

Gnomad ASJ AF: 0.00749

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.000942

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00513

Gnomad OTH AF: 0.00526

GnomAD2 exomes AF: 0.00379 AC: 952 AN: 251444 AF XY: 0.00402

Gnomad AFR exome AF: 0.00148

Gnomad AMR exome AF: 0.00431

Gnomad ASJ exome AF: 0.00695

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00125

Gnomad NFE exome AF: 0.00551

Gnomad OTH exome AF: 0.00538

GnomAD4 exome AF: 0.00523 AC: 7646 AN: 1461874 Hom.: 25 Cov.: 31 AF XY: 0.00512 AC XY: 3727 AN XY: 727240

African (AFR) AF: 0.00102 AC: 34 AN: 33480

American (AMR) AF: 0.00501 AC: 224 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00601 AC: 157 AN: 26134

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.000904 AC: 78 AN: 86254

European-Finnish (FIN) AF: 0.00155 AC: 83 AN: 53420

Middle Eastern (MID) AF: 0.00416 AC: 24 AN: 5768

European-Non Finnish (NFE) AF: 0.00607 AC: 6745 AN: 1112004

Other (OTH) AF: 0.00497 AC: 300 AN: 60396

GnomAD4 genome AF: 0.00353 AC: 537 AN: 152306 Hom.: 3 Cov.: 32 AF XY: 0.00312 AC XY: 232 AN XY: 74468

African (AFR) AF: 0.00130 AC: 54 AN: 41562

American (AMR) AF: 0.00523 AC: 80 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00749 AC: 26 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5182

South Asian (SAS) AF: 0.000622 AC: 3 AN: 4824

European-Finnish (FIN) AF: 0.000942 AC: 10 AN: 10618

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.00515 AC: 350 AN: 68026

Other (OTH) AF: 0.00520 AC: 11 AN: 2114

Alfa AF: 0.00491 Hom.: 5

Bravo AF: 0.00388

TwinsUK AF: 0.00458 AC: 17

ALSPAC AF: 0.00675 AC: 26

ESP6500AA AF: 0.000681 AC: 3

ESP6500EA AF: 0.00500 AC: 43

ExAC AF: 0.00369 AC: 448

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.00720

EpiControl AF: 0.00622

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.089
BayesDel_addAF	Benign	-0.60	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.092	T
Eigen	Benign	-0.17
Eigen_PC	Benign	-0.20
FATHMM_MKL	Benign	0.40	N
LIST_S2	Benign	0.68	T
M_CAP	Benign	0.0092	T
MetaRNN	Benign	0.0056	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	1.4	L
PhyloP100		-0.058
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.097
Sift	Benign	0.34	T
Sift4G	Uncertain	0.022	D
Polyphen		0.99	D
Vest4		0.064
MVP		0.51
MPC		0.22
ClinPred		0.021	T
GERP RS		3.9
Varity_R		0.054
gMVP		0.50
Mutation Taster		=99/1	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: rs150724096; hg19: chr12-56230980; COSMIC: COSV106098757; COSMIC: COSV106098757;