NM_002424.3:c.95C>T

Variant names:

• chr11-102724761-G-A
• rs3765620
• NM_002424.3:c.95C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_002424.3(MMP8):​c.95C>T​(p.Thr32Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.57 in 1,586,530 control chromosomes in the GnomAD database, including 261,255 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.63 (30389 hom., cov: 33)
  • Exomes 𝑓: 0.56 (230866 hom.)
• Consequence: MMP8 NM_002424.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.684
• Publications: 50 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=4.8309057E-6).
• BP6: Variant 11-102724761-G-A is Benign according to our data. Variant chr11-102724761-G-A is described in ClinVar as Benign. ClinVar VariationId is 403100.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.749 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MMP8	NM_002424.3	MANE Select	c.95C>T	p.Thr32Ile	missense	Exon 1 of 10	NP_002415.1
	MMP8	NM_001304441.2		c.-66C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 11	NP_001291370.1
	MMP8	NM_001304442.2		c.-63C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 11	NP_001291371.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MMP8	ENST00000236826.8	TSL:1 MANE Select	c.95C>T	p.Thr32Ile	missense	Exon 1 of 10	ENSP00000236826.3
	MMP8	ENST00000438475.2	TSL:5	c.20C>T	p.Thr7Ile	missense	Exon 1 of 9	ENSP00000401004.2
	MMP8	ENST00000528662.6	TSL:5	n.95C>T		non_coding_transcript_exon	Exon 2 of 12	ENSP00000431431.2

Frequencies

GnomAD3 genomes AF: 0.626 AC: 95189 AN: 151996 Hom.: 30368 Cov.: 33

Gnomad AFR AF: 0.756

Gnomad AMI AF: 0.591

Gnomad AMR AF: 0.587

Gnomad ASJ AF: 0.607

Gnomad EAS AF: 0.633

Gnomad SAS AF: 0.631

Gnomad FIN AF: 0.610

Gnomad MID AF: 0.742

Gnomad NFE AF: 0.558

Gnomad OTH AF: 0.635

GnomAD2 exomes AF: 0.592 AC: 144728 AN: 244278 AF XY: 0.591

Gnomad AFR exome AF: 0.761

Gnomad AMR exome AF: 0.551

Gnomad ASJ exome AF: 0.613

Gnomad EAS exome AF: 0.636

Gnomad FIN exome AF: 0.598

Gnomad NFE exome AF: 0.565

Gnomad OTH exome AF: 0.605

GnomAD4 exome AF: 0.564 AC: 809126 AN: 1434416 Hom.: 230866 Cov.: 31 AF XY: 0.565 AC XY: 402936 AN XY: 712980

African (AFR) AF: 0.765 AC: 25187 AN: 32918

American (AMR) AF: 0.553 AC: 23828 AN: 43124

Ashkenazi Jewish (ASJ) AF: 0.619 AC: 15844 AN: 25578

East Asian (EAS) AF: 0.680 AC: 26618 AN: 39148

South Asian (SAS) AF: 0.611 AC: 49741 AN: 81358

European-Finnish (FIN) AF: 0.591 AC: 31151 AN: 52686

Middle Eastern (MID) AF: 0.699 AC: 3965 AN: 5670

European-Non Finnish (NFE) AF: 0.546 AC: 598127 AN: 1094788

Other (OTH) AF: 0.586 AC: 34665 AN: 59146

GnomAD4 genome AF: 0.626 AC: 95245 AN: 152114 Hom.: 30389 Cov.: 33 AF XY: 0.628 AC XY: 46710 AN XY: 74378

African (AFR) AF: 0.756 AC: 31378 AN: 41500

American (AMR) AF: 0.586 AC: 8957 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.607 AC: 2104 AN: 3464

East Asian (EAS) AF: 0.634 AC: 3282 AN: 5176

South Asian (SAS) AF: 0.629 AC: 3036 AN: 4828

European-Finnish (FIN) AF: 0.610 AC: 6446 AN: 10570

Middle Eastern (MID) AF: 0.740 AC: 216 AN: 292

European-Non Finnish (NFE) AF: 0.558 AC: 37942 AN: 67976

Other (OTH) AF: 0.636 AC: 1345 AN: 2114

Alfa AF: 0.582 Hom.: 119175

Bravo AF: 0.629

TwinsUK AF: 0.529 AC: 1961

ALSPAC AF: 0.554 AC: 2136

ESP6500AA AF: 0.751 AC: 3309

ESP6500EA AF: 0.557 AC: 4788

ExAC AF: 0.597 AC: 72457

Asia WGS AF: 0.662 AC: 2299 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency

not provided Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.062
BayesDel_addAF	Benign	-0.69	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	4.0
DANN	Benign	0.95
DEOGEN2	Benign	0.028	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.00022	N
LIST_S2	Benign	0.0083	T
MetaRNN	Benign	0.0000048	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	-1.1	N
PhyloP100		0.68
PrimateAI	Benign	0.36	T
PROVEAN	Benign	2.3	N
REVEL	Benign	0.052
Sift	Benign	0.27	T
Sift4G	Benign	0.42	T
Polyphen		0.0	B
Vest4		0.022
MPC		0.041
ClinPred		0.0031	T
GERP RS		0.96
PromoterAI		-0.027	Neutral
Varity_R		0.037
gMVP		0.18
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3765620; hg19: chr11-102595492; COSMIC: COSV99030574;