14-22837130-C-T

Variant names:

• chr14-22837130-C-T
• rs531618881
• NM_004995.4:c.108+205C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_004995.4(MMP14):​c.108+205C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00827 in 690,978 control chromosomes in the GnomAD database, including 238 homozygotes. In-silico tool predicts a benign outcome for this variant. 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0210
• 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BP6: Variant 14-22837130-C-T is Benign according to our data. Variant chr14-22837130-C-T is described in ClinVar as Benign. ClinVar VariationId is 1235474.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 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+205C>T		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+205C>T		intron	N/A	ENSP00000308208.6	P50281
	MMP14	ENST00000928197.1		c.108+205C>T		intron	N/A	ENSP00000598256.1
	MMP14	ENST00000548162.2	TSL:5	c.108+205C>T		intron	N/A	ENSP00000506068.1	A0A7P0TAG0

Frequencies

GnomAD3 genomes AF: 0.0256 AC: 3892 AN: 152094 Hom.: 159 Cov.: 32

Gnomad AFR AF: 0.0897

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00884

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: 0.00338 AC: 1820 AN: 538766 Hom.: 79 Cov.: 3 AF XY: 0.00279 AC XY: 813 AN XY: 291310

African (AFR) AF: 0.0908 AC: 1406 AN: 15488

American (AMR) AF: 0.00476 AC: 163 AN: 34262

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19684

East Asian (EAS) AF: 0.00 AC: 0 AN: 31464

South Asian (SAS) AF: 0.000227 AC: 14 AN: 61642

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32872

Middle Eastern (MID) AF: 0.00305 AC: 12 AN: 3936

European-Non Finnish (NFE) AF: 0.000116 AC: 36 AN: 309484

Other (OTH) AF: 0.00631 AC: 189 AN: 29934

GnomAD4 genome AF: 0.0256 AC: 3895 AN: 152212 Hom.: 159 Cov.: 32 AF XY: 0.0245 AC XY: 1826 AN XY: 74428

African (AFR) AF: 0.0895 AC: 3715 AN: 41496

American (AMR) AF: 0.00876 AC: 134 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

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

European-Non Finnish (NFE) AF: 0.000176 AC: 12 AN: 68010

Other (OTH) AF: 0.0152 AC: 32 AN: 2112

Alfa AF: 0.0213 Hom.: 5

Bravo AF: 0.0288

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	12
DANN	Benign	0.94
PhyloP100		-0.021
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs531618881; hg19: chr14-23306339;