chr14-22843385-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_004995.4(MMP14):ā€‹c.817G>Cā€‹(p.Asp273His) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,676 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. D273N) has been classified as Benign.

Frequency

Genomes: not found (cov: 31)
Exomes š‘“: 0.0000021 ( 0 hom. )

Consequence

MMP14
NM_004995.4 missense

Scores

1
4
14

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.88
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
MMP14NM_004995.4 linkuse as main transcriptc.817G>C p.Asp273His missense_variant 5/10 ENST00000311852.11

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
MMP14ENST00000311852.11 linkuse as main transcriptc.817G>C p.Asp273His missense_variant 5/101 NM_004995.4 P1
MMP14ENST00000548162.2 linkuse as main transcriptc.817G>C p.Asp273His missense_variant 5/105
MMP14ENST00000680097.1 linkuse as main transcriptc.*132G>C 3_prime_UTR_variant, NMD_transcript_variant 5/10
MMP14ENST00000680941.1 linkuse as main transcriptc.*215G>C 3_prime_UTR_variant, NMD_transcript_variant 6/11

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
AF:
0.00000205
AC:
3
AN:
1461676
Hom.:
0
Cov.:
34
AF XY:
0.00000275
AC XY:
2
AN XY:
727150
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000671
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.:
31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.39
BayesDel_addAF
Benign
-0.15
T
BayesDel_noAF
Benign
-0.45
CADD
Uncertain
24
DANN
Benign
0.79
DEOGEN2
Benign
0.080
T
Eigen
Benign
0.010
Eigen_PC
Benign
0.13
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.88
D
M_CAP
Benign
0.019
T
MetaRNN
Uncertain
0.55
D
MetaSVM
Benign
-1.1
T
MutationAssessor
Uncertain
2.0
M
MutationTaster
Benign
0.0000020
P
PrimateAI
Benign
0.41
T
PROVEAN
Benign
-1.8
N
REVEL
Benign
0.084
Sift
Benign
0.25
T
Sift4G
Benign
0.13
T
Polyphen
0.015
B
Vest4
0.36
MutPred
0.51
Gain of catalytic residue at D275 (P = 0.02);
MVP
0.28
MPC
0.63
ClinPred
0.79
D
GERP RS
5.6
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.49
gMVP
0.62

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1042704; hg19: chr14-23312594; API