rs1003349

Variant names:

• chr14-22836454-G-C
• rs1003349
• NM_004995.4:c.-364G>C

Your query was ambiguous. Multiple possible variants found:

• chr14-22836454-G-C
• chr14-22836454-G-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_004995.4(MMP14):​c.-364G>C variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 28)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MMP14 NM_004995.4 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.556
• Publications: 28 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: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
• multicentric osteolysis-nodulosis-arthropathy spectrum

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).

Transcripts

RefSeq

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

Ensembl

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

Frequencies

GnomAD3 genomes Cov.: 28

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 55980 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 28836

African (AFR) AF: 0.00 AC: 0 AN: 2044

American (AMR) AF: 0.00 AC: 0 AN: 1460

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2006

East Asian (EAS) AF: 0.00 AC: 0 AN: 3788

South Asian (SAS) AF: 0.00 AC: 0 AN: 624

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 3948

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 326

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 38106

Other (OTH) AF: 0.00 AC: 0 AN: 3678

GnomAD4 genome Cov.: 28

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	8.0
DANN	Benign	0.54
PhyloP100		0.56
PromoterAI		-0.013	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1003349; hg19: chr14-23305663;