14-22836839-C-T

Position:

chr14-22836839-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000311852.11(MMP14):c.22C>T(p.Pro8Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.844 in 1,611,232 control chromosomes in the GnomAD database, including 575,345 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.85 ( 54474 hom., cov: 30)

Exomes 𝑓: 0.84 ( 520871 hom. )

Consequence

MMP14
ENST00000311852.11 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.424

Variant links:

Genes affected

MMP14 (HGNC:7160): (matrix metallopeptidase 14) Proteins of the matrix metalloproteinase (MMP) family 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. Most MMP's are secreted as inactive proproteins which are activated when cleaved by extracellular proteinases. However, the protein encoded by this gene is a member of the membrane-type MMP (MT-MMP) subfamily; each member of this subfamily contains a potential transmembrane domain suggesting that these proteins are expressed at the cell surface rather than secreted. This protein activates MMP2 protein, and this activity may be involved in tumor invasion. [provided by RefSeq, Jul 2008]

MMP14 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=7.0322017E-7).

BP6

Variant 14-22836839-C-T is Benign according to our data. Variant chr14-22836839-C-T is described in ClinVar as [Benign]. Clinvar id is 1279198.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.974 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MMP14	NM_004995.4 linkuse as main transcript	c.22C>T	p.Pro8Ser	missense_variant	1/10	ENST00000311852.11	NP_004986.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MMP14	ENST00000311852.11 linkuse as main transcript	c.22C>T	p.Pro8Ser	missense_variant	1/10	1	NM_004995.4	ENSP00000308208	P1

Frequencies

GnomAD3 genomes

AF:

0.846

AC:

128389

AN:

151806

Hom.:

54425

Cov.:

show subpopulations

Gnomad AFR

AF:

0.830

Gnomad AMI

AF:

0.668

Gnomad AMR

AF:

0.854

Gnomad ASJ

AF:

0.835

Gnomad EAS

AF:

0.997

Gnomad SAS

AF:

0.782

Gnomad FIN

AF:

0.883

Gnomad MID

AF:

0.810

Gnomad NFE

AF:

0.844

Gnomad OTH

AF:

0.847

GnomAD3 exomes

AF:

0.856

AC:

209568

AN:

244772

Hom.:

90065

AF XY:

0.849

AC XY:

112883

AN XY:

132986

show subpopulations

Gnomad AFR exome

AF:

0.831

Gnomad AMR exome

AF:

0.885

Gnomad ASJ exome

AF:

0.834

Gnomad EAS exome

AF:

0.998

Gnomad SAS exome

AF:

0.774

Gnomad FIN exome

AF:

0.880

Gnomad NFE exome

AF:

0.847

Gnomad OTH exome

AF:

0.851

GnomAD4 exome

AF:

0.844

AC:

1231649

AN:

1459308

Hom.:

520871

Cov.:

AF XY:

0.842

AC XY:

610839

AN XY:

725830

show subpopulations

Gnomad4 AFR exome

AF:

0.836

Gnomad4 AMR exome

AF:

0.882

Gnomad4 ASJ exome

AF:

0.832

Gnomad4 EAS exome

AF:

0.999

Gnomad4 SAS exome

AF:

0.769

Gnomad4 FIN exome

AF:

0.878

Gnomad4 NFE exome

AF:

0.842

Gnomad4 OTH exome

AF:

0.845

GnomAD4 genome

AF:

0.846

AC:

128497

AN:

151924

Hom.:

54474

Cov.:

AF XY:

0.847

AC XY:

62904

AN XY:

74262

show subpopulations

Gnomad4 AFR

AF:

0.830

Gnomad4 AMR

AF:

0.854

Gnomad4 ASJ

AF:

0.835

Gnomad4 EAS

AF:

0.997

Gnomad4 SAS

AF:

0.783

Gnomad4 FIN

AF:

0.883

Gnomad4 NFE

AF:

0.844

Gnomad4 OTH

AF:

0.849

Alfa

AF:

0.844

Hom.:

64955

Bravo

AF:

0.846

TwinsUK

AF:

0.831

AC:

3083

ALSPAC

AF:

0.838

AC:

3230

ESP6500AA

AF:

0.825

AC:

3636

ESP6500EA

AF:

0.839

AC:

7214

ExAC

AF:

0.851

AC:

103129

Asia WGS

AF:

0.919

AC:

3196

AN:

3478

EpiCase

AF:

0.839

EpiControl

AF:

0.845

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 19, 2019	- -

MMP14-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Sep 09, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.067

BayesDel_addAF

Benign

-0.71

BayesDel_noAF

Benign

-0.65

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.048

Eigen

Benign

-0.97

Eigen_PC

Benign

-0.82

FATHMM_MKL

Benign

0.029

LIST_S2

Benign

0.12

MetaRNN

Benign

7.0e-7

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.0

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.58

PROVEAN

Benign

0.68

REVEL

Benign

0.062

Sift

Benign

1.0

Sift4G

Benign

0.93

Polyphen

0.0

Vest4

0.025

MPC

0.67

ClinPred

0.0051

GERP RS

2.5

Varity_R

0.028

gMVP

0.29

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