14-22837127-TGC-T

Position:

• chr14-22837127-TGC-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_004995.4(MMP14):​c.108+203_108+204del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00829 in 688,848 control chromosomes in the GnomAD database, including 238 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.026 (159 hom., cov: 32)
  • Exomes 𝑓: 0.0034 (79 hom.)
• Consequence: MMP14 NM_004995.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.345

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 14-22837127-TGC-T is Benign according to our data. Variant chr14-22837127-TGC-T is described in ClinVar as [Benign]. Clinvar id is 1182053.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0871 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MMP14	NM_004995.4	c.108+203_108+204del		intron_variant		ENST00000311852.11	NP_004986.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MMP14	ENST00000311852.11	c.108+203_108+204del		intron_variant		1	NM_004995.4	ENSP00000308208	P1

Frequencies

GnomAD3 genomes AF: 0.0256 AC: 3891 AN: 152060 Hom.: 159 Cov.: 32

Gnomad AFR AF: 0.0896

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00878

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000176

Gnomad OTH AF: 0.0153

GnomAD4 exome AF: 0.00339 AC: 1818 AN: 536670 Hom.: 79 AF XY: 0.00280 AC XY: 812 AN XY: 290174

Gnomad4 AFR exome AF: 0.0911

Gnomad4 AMR exome AF: 0.00478

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000211

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000117

Gnomad4 OTH exome AF: 0.00635

GnomAD4 genome AF: 0.0256 AC: 3894 AN: 152178 Hom.: 159 Cov.: 32 AF XY: 0.0245 AC XY: 1825 AN XY: 74410

Gnomad4 AFR AF: 0.0895

Gnomad4 AMR AF: 0.00870

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000176

Gnomad4 OTH AF: 0.0152

Alfa AF: 0.0214 Hom.: 6

Asia WGS AF: 0.00577 AC: 20 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 24, 2021

- -

Computational scores

Source: dbNSFP v4.3

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: rs10543628; hg19: chr14-23306336;