Genetic Variant MMP8:p.His432Gln (chr11-102713456-A-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_002424.3(MMP8):c.1296T>A(p.His432Gln) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000256 in 1,603,626 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 18/24 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000026 ( 0 hom. )

Consequence

MMP8
NM_002424.3 missense, splice_region

Scores

Splicing: ADA: 0.0003585

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.34

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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.022199601).

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.1296T>A	p.His432Gln	missense splice_region	Exon 10 of 10	NP_002415.1	P22894
MMP8	NM_001304441.2		c.1227T>A	p.His409Gln	missense splice_region	Exon 11 of 11	NP_001291370.1
MMP8	NM_001304442.2		c.1227T>A	p.His409Gln	missense splice_region	Exon 11 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.1296T>A	p.His432Gln	missense splice_region	Exon 10 of 10	ENSP00000236826.3	P22894
MMP8	ENST00000438475.2	TSL:5	c.*35T>A		splice_region	Exon 9 of 9	ENSP00000401004.2	H7C1M3
MMP8	ENST00000438475.2	TSL:5	c.*35T>A		3_prime_UTR	Exon 9 of 9	ENSP00000401004.2	H7C1M3

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152228

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

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:

0.000478

GnomAD2 exomes

AF:

0.000124

AC:

AN:

249964

AF XY:

0.000118

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000901

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000262

AC:

AN:

1451398

Hom.:

Cov.:

AF XY:

0.0000235

AC XY:

AN XY:

722816

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33240

American (AMR)

AF:

0.000807

AC:

AN:

44626

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26066

East Asian (EAS)

AF:

0.00

AC:

AN:

39576

South Asian (SAS)

AF:

0.00

AC:

AN:

85932

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53376

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5744

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1102780

Other (OTH)

AF:

0.0000333

AC:

AN:

60058

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152228

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74362

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41460

American (AMR)

AF:

0.000131

AC:

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5206

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68034

Other (OTH)

AF:

0.000478

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000604

ExAC

AF:

0.000115

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.72

CADD

Benign

7.9

(source)

DANN

Benign

0.84

DEOGEN2

Benign

0.073

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.033

LIST_S2

Benign

0.13

M_CAP

Benign

0.0036

MetaRNN

Benign

0.022

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.92

PhyloP100

-1.3

PrimateAI

Benign

0.29

PROVEAN

Benign

-0.49

REVEL

Benign

0.026

Sift

Uncertain

0.0030

Sift4G

Uncertain

0.011

Polyphen

0.0060

Vest4

0.078

MutPred

0.52

Loss of catalytic residue at Q429 (P = 0.0505)

MVP

0.13

MPC

0.041

ClinPred

0.039

GERP RS

-5.4

Varity_R

0.081

gMVP

0.21

Mutation Taster

=98/2

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00036

dbscSNV1_RF

Benign

0.012

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

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

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over