rs1042703

Variant names:

• chr14-22836839-C-A
• rs1042703
• NM_004995.4:c.22C>A

Your query was ambiguous. Multiple possible variants found:

• chr14-22836839-C-A
• chr14-22836839-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_004995.4(MMP14):​c.22C>A​(p.Pro8Thr) variant causes a missense 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. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P8S) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MMP14 NM_004995.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.424

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.03638056).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MMP14	NM_004995.4	c.22C>A	p.Pro8Thr	missense_variant	Exon 1 of 10	ENST00000311852.11	NP_004986.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MMP14	ENST00000311852.11	c.22C>A	p.Pro8Thr	missense_variant	Exon 1 of 10	1	NM_004995.4	ENSP00000308208.6

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1459436 Hom.: 0 Cov.: 42 AF XY: 0.00 AC XY: 0 AN XY: 725892

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	12
DANN	Benign	0.95
DEOGEN2	Benign	0.048	T
Eigen	Benign	-0.95
Eigen_PC	Benign	-0.80
FATHMM_MKL	Benign	0.066	N
LIST_S2	Benign	0.15	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.036	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.0	N
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	0.51	N
REVEL	Benign	0.043
Sift	Benign	0.42	T
Sift4G	Benign	0.70	T
Polyphen		0.0	B
Vest4		0.064
MutPred		0.29		Gain of catalytic residue at L11 (P = 6e-04);
MVP		0.24
MPC		0.74
ClinPred		0.053	T
GERP RS		2.5
Varity_R		0.038
gMVP		0.36

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: rs1042703; hg19: chr14-23306048;