14-22837127-TGC-T

Variant names:

• chr14-22837127-TGC-T
• rs10543628
• NM_004995.4:c.108+203_108+204delGC

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_004995.4(MMP14):​c.108+203_108+204delGC 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
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• Winchester syndrome

  Inheritance: AR, Unknown Classification: MODERATE, LIMITED Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• multicentric osteolysis-nodulosis-arthropathy spectrum

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004995.4. 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
	MMP14	NM_004995.4	MANE Select	c.108+203_108+204delGC		intron	N/A	NP_004986.1	P50281

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MMP14	ENST00000311852.11	TSL:1 MANE Select	c.108+203_108+204delGC		intron	N/A	ENSP00000308208.6	P50281
	MMP14	ENST00000928197.1		c.108+203_108+204delGC		intron	N/A	ENSP00000598256.1
	MMP14	ENST00000548162.2	TSL:5	c.108+203_108+204delGC		intron	N/A	ENSP00000506068.1	A0A7P0TAG0

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

African (AFR) AF: 0.0911 AC: 1405 AN: 15418

American (AMR) AF: 0.00478 AC: 163 AN: 34102

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19626

East Asian (EAS) AF: 0.00 AC: 0 AN: 31334

South Asian (SAS) AF: 0.000211 AC: 13 AN: 61608

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32750

Middle Eastern (MID) AF: 0.00305 AC: 12 AN: 3940

European-Non Finnish (NFE) AF: 0.000117 AC: 36 AN: 308122

Other (OTH) AF: 0.00635 AC: 189 AN: 29770

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

African (AFR) AF: 0.0895 AC: 3715 AN: 41506

American (AMR) AF: 0.00870 AC: 133 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000176 AC: 12 AN: 67998

Other (OTH) AF: 0.0152 AC: 32 AN: 2110

Alfa AF: 0.0214 Hom.: 6

Asia WGS AF: 0.00577 AC: 20 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.34
Mutation Taster		=100/0	polymorphism (auto)

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: rs10543628; hg19: chr14-23306336;