Genetic Variant NM_004995.4:c.-364G>T (chr14-22836454-G-T) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_004995.4(MMP14):c.-364G>T variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.277 in 205,110 control chromosomes in the GnomAD database, including 8,633 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.30 ( 7000 hom., cov: 28)

Exomes 𝑓: 0.22 ( 1633 hom. )

Consequence

MMP14
NM_004995.4 upstream_gene

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.556

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 14-22836454-G-T is Benign according to our data. Variant chr14-22836454-G-T is described in ClinVar as [Benign]. Clinvar id is 1297228.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.407 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MMP14	NM_004995.4 link	c.-364G>T		upstream_gene_variant		ENST00000311852.11	NP_004986.1	P50281

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MMP14	ENST00000311852.11 link	c.-364G>T		upstream_gene_variant		1	NM_004995.4	ENSP00000308208.6		P50281

Frequencies

GnomAD3 genomes

AF:

0.297

AC:

44369

AN:

149290

Hom.:

7003

Cov.:

show subpopulations

Gnomad AFR

AF:

0.214

Gnomad AMI

AF:

0.210

Gnomad AMR

AF:

0.411

Gnomad ASJ

AF:

0.398

Gnomad EAS

AF:

0.423

Gnomad SAS

AF:

0.294

Gnomad FIN

AF:

0.358

Gnomad MID

AF:

0.318

Gnomad NFE

AF:

0.299

Gnomad OTH

AF:

0.317

GnomAD4 exome

AF:

0.222

AC:

12355

AN:

55706

Hom.:

1633

AF XY:

0.224

AC XY:

6430

AN XY:

28706

show subpopulations

Gnomad4 AFR exome

AF:

0.148

Gnomad4 AMR exome

AF:

0.332

Gnomad4 ASJ exome

AF:

0.272

Gnomad4 EAS exome

AF:

0.328

Gnomad4 SAS exome

AF:

0.158

Gnomad4 FIN exome

AF:

0.237

Gnomad4 NFE exome

AF:

0.209

Gnomad4 OTH exome

AF:

0.212

GnomAD4 genome

AF:

0.297

AC:

44380

AN:

149404

Hom.:

7000

Cov.:

AF XY:

0.303

AC XY:

22061

AN XY:

72694

show subpopulations

Gnomad4 AFR

AF:

0.214

Gnomad4 AMR

AF:

0.411

Gnomad4 ASJ

AF:

0.398

Gnomad4 EAS

AF:

0.422

Gnomad4 SAS

AF:

0.294

Gnomad4 FIN

AF:

0.358

Gnomad4 NFE

AF:

0.299

Gnomad4 OTH

AF:

0.313

Alfa

AF:

0.306

Hom.:

10762

Bravo

AF:

0.300

Asia WGS

AF:

0.347

AC:

1202

AN:

3470

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

May 14, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 18927121) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

8.2

DANN

Benign

0.62

Splicing

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