11-102713373-T-G

Position:

• chr11-102713373-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002424.3(MMP8):​c.1379A>C​(p.Lys460Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0575 in 1,612,716 control chromosomes in the GnomAD database, including 3,936 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 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 nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.094 (1094 hom., cov: 33)
  • Exomes 𝑓: 0.054 (2842 hom.)
• Consequence: MMP8 NM_002424.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.322

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0028057992).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.205 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MMP8	NM_002424.3	c.1379A>C	p.Lys460Thr	missense_variant	10/10	ENST00000236826.8	NP_002415.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MMP8	ENST00000236826.8	c.1379A>C	p.Lys460Thr	missense_variant	10/10	1	NM_002424.3	ENSP00000236826	P1
MMP8	ENST00000438475.2	c.*118A>C		3_prime_UTR_variant	9/9	5		ENSP00000401004
MMP8	ENST00000528662.6	c.*1356A>C		3_prime_UTR_variant, NMD_transcript_variant	12/12	5		ENSP00000431431

Frequencies

GnomAD3 genomes AF: 0.0943 AC: 14346 AN: 152130 Hom.: 1089 Cov.: 33

Gnomad AFR AF: 0.209

Gnomad AMI AF: 0.0351

Gnomad AMR AF: 0.0577

Gnomad ASJ AF: 0.0637

Gnomad EAS AF: 0.00885

Gnomad SAS AF: 0.0577

Gnomad FIN AF: 0.0520

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.0511

Gnomad OTH AF: 0.0880

GnomAD3 exomes AF: 0.0604 AC: 15146 AN: 250740 Hom.: 728 AF XY: 0.0583 AC XY: 7894 AN XY: 135482

Gnomad AFR exome AF: 0.206

Gnomad AMR exome AF: 0.0382

Gnomad ASJ exome AF: 0.0674

Gnomad EAS exome AF: 0.00757

Gnomad SAS exome AF: 0.0605

Gnomad FIN exome AF: 0.0517

Gnomad NFE exome AF: 0.0552

Gnomad OTH exome AF: 0.0720

GnomAD4 exome AF: 0.0536 AC: 78330 AN: 1460468 Hom.: 2842 Cov.: 31 AF XY: 0.0536 AC XY: 38968 AN XY: 726630

Gnomad4 AFR exome AF: 0.218

Gnomad4 AMR exome AF: 0.0403

Gnomad4 ASJ exome AF: 0.0657

Gnomad4 EAS exome AF: 0.00565

Gnomad4 SAS exome AF: 0.0604

Gnomad4 FIN exome AF: 0.0527

Gnomad4 NFE exome AF: 0.0494

Gnomad4 OTH exome AF: 0.0625

GnomAD4 genome AF: 0.0944 AC: 14377 AN: 152248 Hom.: 1094 Cov.: 33 AF XY: 0.0933 AC XY: 6947 AN XY: 74432

Gnomad4 AFR AF: 0.209

Gnomad4 AMR AF: 0.0576

Gnomad4 ASJ AF: 0.0637

Gnomad4 EAS AF: 0.00887

Gnomad4 SAS AF: 0.0580

Gnomad4 FIN AF: 0.0520

Gnomad4 NFE AF: 0.0511

Gnomad4 OTH AF: 0.0870

Alfa AF: 0.0599 Hom.: 679

Bravo AF: 0.0994

TwinsUK AF: 0.0464 AC: 172

ALSPAC AF: 0.0444 AC: 171

ESP6500AA AF: 0.200 AC: 879

ESP6500EA AF: 0.0536 AC: 461

ExAC AF: 0.0661 AC: 8026

Asia WGS AF: 0.0450 AC: 158 AN: 3478

EpiCase AF: 0.0587

EpiControl AF: 0.0599

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.83	T
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.6
DANN	Benign	0.87
DEOGEN2	Benign	0.055	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.037	N
LIST_S2	Benign	0.19	T
MetaRNN	Benign	0.0028	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.035	N
MutationTaster	Benign	1.0	P
PrimateAI	Benign	0.29	T
PROVEAN	Benign	0.020	N
REVEL	Benign	0.012
Sift	Benign	0.16	T
Sift4G	Benign	0.21	T
Polyphen		0.0020	B
Vest4		0.086
MPC		0.045
ClinPred		0.0028	T
GERP RS		-8.0
Varity_R		0.045
gMVP		0.45

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

LitVar

Other links and lift over

dbSNP: rs35866072; hg19: chr11-102584104; COSMIC: COSV52632606;