Genetic Variant NM_002424.3:c.1096T>C (chr11-102714650-A-G) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_002424.3(MMP8):c.1096T>C(p.Ser366Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000712 in 1,404,852 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. S366T) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 30)

Exomes 𝑓: 7.1e-7 ( 0 hom. )

Consequence

MMP8
NM_002424.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.106

Publications

0 publications found

Variant links:

Genes affected

MMP8 (HGNC:7175): (matrix metallopeptidase 8) This gene encodes a member of the matrix metalloproteinase (MMP) family of proteins. These proteins are involved in the breakdown of extracellular matrix in embryonic development, reproduction, and tissue remodeling, as well as in disease processes, such as arthritis and metastasis. Proteolysis at different sites on this protein results in multiple active forms of the enzyme with distinct N-termini. This protein functions in the degradation of type I, II and III collagens. The gene is part of a cluster of MMP genes which localize to chromosome 11q22.3. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2015]

MMP8 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002424.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MMP8	NM_002424.3	MANE Select	c.1096T>C	p.Ser366Pro	missense	Exon 8 of 10	NP_002415.1	P22894
MMP8	NM_001304441.2		c.1027T>C	p.Ser343Pro	missense	Exon 9 of 11	NP_001291370.1
MMP8	NM_001304442.2		c.1027T>C	p.Ser343Pro	missense	Exon 9 of 11	NP_001291371.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MMP8	ENST00000236826.8	TSL:1 MANE Select	c.1096T>C	p.Ser366Pro	missense	Exon 8 of 10	ENSP00000236826.3	P22894
MMP8	ENST00000438475.2	TSL:5	c.961+654T>C		intron	N/A	ENSP00000401004.2	H7C1M3
MMP8	ENST00000528662.6	TSL:5	n.*1073T>C		non_coding_transcript_exon	Exon 10 of 12	ENSP00000431431.2	E9PL87

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.12e-7

AC:

AN:

1404852

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

698040

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.0000332

AC:

AN:

30146

American (AMR)

AF:

0.00

AC:

AN:

35206

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24934

East Asian (EAS)

AF:

0.00

AC:

AN:

34580

South Asian (SAS)

AF:

0.00

AC:

AN:

76992

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52684

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5640

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1086792

Other (OTH)

AF:

0.00

AC:

AN:

57878

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.225

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.28

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.46

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.14

Eigen

Benign

-0.25

Eigen_PC

Benign

-0.48

FATHMM_MKL

Benign

0.075

LIST_S2

Benign

0.61

M_CAP

Benign

0.010

MetaRNN

Uncertain

0.74

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.8

PhyloP100

-0.11

PrimateAI

Benign

0.34

PROVEAN

Uncertain

-2.5

REVEL

Benign

0.16

Sift

Uncertain

0.023

Sift4G

Uncertain

0.044

Polyphen

0.94

Vest4

0.60

MutPred

0.63

Gain of methylation at K363 (P = 0.0648)

MVP

0.39

MPC

0.27

ClinPred

0.91

GERP RS

0.23

Varity_R

0.31

gMVP

0.73

Mutation Taster

=90/10

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over