Variant chr12-55837196-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

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. 14/21 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

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0580

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 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 id is 773261.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 537 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MMP19	NM_002429.6 linkuse as main transcript	c.1367G>A	p.Arg456Gln	missense_variant	9/9	ENST00000322569.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MMP19	ENST00000322569.9 linkuse as main transcript	c.1367G>A	p.Arg456Gln	missense_variant	9/9	1	NM_002429.6	P1	Q99542-1

Frequencies

GnomAD3 genomes

AF:

0.00352

AC:

536

AN:

152188

Hom.:

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.00379

AC:

952

AN:

251444

Hom.:

AF XY:

0.00402

AC XY:

546

AN XY:

135894

show subpopulations

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 SAS exome

AF:

0.000686

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.:

Cov.:

AF XY:

0.00512

AC XY:

3727

AN XY:

727240

show subpopulations

Gnomad4 AFR exome

AF:

0.00102

Gnomad4 AMR exome

AF:

0.00501

Gnomad4 ASJ exome

AF:

0.00601

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000904

Gnomad4 FIN exome

AF:

0.00155

Gnomad4 NFE exome

AF:

0.00607

Gnomad4 OTH exome

AF:

0.00497

GnomAD4 genome

AF:

0.00353

AC:

537

AN:

152306

Hom.:

Cov.:

AF XY:

0.00312

AC XY:

232

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.00130

Gnomad4 AMR

AF:

0.00523

Gnomad4 ASJ

AF:

0.00749

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.000622

Gnomad4 FIN

AF:

0.000942

Gnomad4 NFE

AF:

0.00515

Gnomad4 OTH

AF:

0.00520

Alfa

AF:

0.00510

Hom.:

Bravo

AF:

0.00388

TwinsUK

AF:

0.00458

AC:

ALSPAC

AF:

0.00675

AC:

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.00500

AC:

ExAC

AF:

0.00369

AC:

448

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00720

EpiControl

AF:

0.00622

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.089

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.63

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.092

T;.

Eigen

Benign

-0.17

Eigen_PC

Benign

-0.20

FATHMM_MKL

Benign

0.40

LIST_S2

Benign

0.68

T;T

M_CAP

Benign

0.0092

MetaRNN

Benign

0.0056

T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

1.4

L;.

MutationTaster

Benign

0.84

D;D;D;D

PrimateAI

Benign

0.23

PROVEAN

Benign

-1.4

N;N

REVEL

Benign

0.097

Sift

Benign

0.34

T;T

Sift4G

Uncertain

0.022

D;D

Polyphen

0.99

D;.

Vest4

0.064

MVP

0.51

MPC

0.22

ClinPred

0.021

GERP RS

3.9

Varity_R

0.054

gMVP

0.50

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over