Genetic Variant MMP8:p.Thr32Ser (chr11-102724761-G-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_002424.3(MMP8):c.95C>G(p.Thr32Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 16/22 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. T32I) has been classified as Benign.

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

MMP8
NM_002424.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.684

Publications

50 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:

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ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (MetaRNN=0.21819621).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MMP8	NM_002424.3 link	c.95C>G	p.Thr32Ser	missense_variant	Exon 1 of 10	ENST00000236826.8	NP_002415.1	P22894

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MMP8	ENST00000236826.8 link	c.95C>G	p.Thr32Ser	missense_variant	Exon 1 of 10	1	NM_002424.3	ENSP00000236826.3		P22894

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

152056

Hom.:

Cov.:

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1438402

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

714846

African (AFR)

AF:

0.00

AC:

AN:

32978

American (AMR)

AF:

0.00

AC:

AN:

43194

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25630

East Asian (EAS)

AF:

0.00

AC:

AN:

39214

South Asian (SAS)

AF:

0.00

AC:

AN:

81578

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52762

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5680

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1098060

Other (OTH)

AF:

0.00

AC:

AN:

59306

GnomAD4 genome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

152056

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74272

African (AFR)

AF:

0.00

AC:

AN:

41406

American (AMR)

AF:

0.00

AC:

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10576

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67996

Other (OTH)

AF:

0.00

AC:

AN:

2092

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.63

CADD

Benign

8.8

(source)

DANN

Benign

0.75

DEOGEN2

Benign

0.058

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.039

LIST_S2

Benign

0.0039

M_CAP

Benign

0.017

MetaRNN

Benign

0.22

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.5

PhyloP100

0.68

PrimateAI

Benign

0.37

PROVEAN

Benign

-0.78

REVEL

Benign

0.034

Sift

Benign

0.059

Sift4G

Benign

0.32

Polyphen

0.0040

Vest4

0.11

MutPred

0.45

Gain of disorder (P = 0.0545);

MVP

0.29

MPC

0.036

ClinPred

0.10

GERP RS

0.96

PromoterAI

-0.035

Neutral

(source)

Varity_R

0.051

gMVP

0.22

Mutation Taster

=98/2

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over