rs2846707

Positions:

• chr11-102705627-T-C

Variant summary

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

The NM_022122.3(MMP27):​c.88A>G​(p.Met30Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.677 in 1,564,006 control chromosomes in the GnomAD database, including 364,507 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 0.74 (42938 hom., cov: 33)
  • Exomes 𝑓: 0.67 (321569 hom.)
• Consequence: MMP27 NM_022122.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.289

Genes affected

MMP27 (HGNC:14250): (matrix metallopeptidase 27) Proteins of the matrix metalloproteinase (MMP) family are involved in the breakdown of extracellular matrix in normal physiological processes, such as embryonic development, reproduction, and tissue remodeling, as well as in disease processes, such as arthritis and metastasis. Most MMP's are secreted as inactive proproteins which are activated when cleaved by extracellular proteinases. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.0296859E-6).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.885 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MMP27	NM_022122.3	c.88A>G	p.Met30Val	missense_variant	1/10	ENST00000260229.5	NP_071405.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MMP27	ENST00000260229.5	c.88A>G	p.Met30Val	missense_variant	1/10	1	NM_022122.3	ENSP00000260229.4

Frequencies

GnomAD3 genomes AF: 0.744 AC: 113060 AN: 152022 Hom.: 42878 Cov.: 33

Gnomad AFR AF: 0.874

Gnomad AMI AF: 0.709

Gnomad AMR AF: 0.740

Gnomad ASJ AF: 0.679

Gnomad EAS AF: 0.907

Gnomad SAS AF: 0.790

Gnomad FIN AF: 0.678

Gnomad MID AF: 0.778

Gnomad NFE AF: 0.663

Gnomad OTH AF: 0.763

GnomAD3 exomes AF: 0.714 AC: 163364 AN: 228792 Hom.: 59471 AF XY: 0.711 AC XY: 88128 AN XY: 123998

Gnomad AFR exome AF: 0.871

Gnomad AMR exome AF: 0.720

Gnomad ASJ exome AF: 0.680

Gnomad EAS exome AF: 0.902

Gnomad SAS exome AF: 0.761

Gnomad FIN exome AF: 0.666

Gnomad NFE exome AF: 0.664

Gnomad OTH exome AF: 0.715

GnomAD4 exome AF: 0.670 AC: 946067 AN: 1411866 Hom.: 321569 Cov.: 26 AF XY: 0.673 AC XY: 473055 AN XY: 703276

Gnomad4 AFR exome AF: 0.878

Gnomad4 AMR exome AF: 0.726

Gnomad4 ASJ exome AF: 0.684

Gnomad4 EAS exome AF: 0.923

Gnomad4 SAS exome AF: 0.764

Gnomad4 FIN exome AF: 0.664

Gnomad4 NFE exome AF: 0.644

Gnomad4 OTH exome AF: 0.695

GnomAD4 genome AF: 0.744 AC: 113175 AN: 152140 Hom.: 42938 Cov.: 33 AF XY: 0.746 AC XY: 55483 AN XY: 74378

Gnomad4 AFR AF: 0.874

Gnomad4 AMR AF: 0.741

Gnomad4 ASJ AF: 0.679

Gnomad4 EAS AF: 0.907

Gnomad4 SAS AF: 0.789

Gnomad4 FIN AF: 0.678

Gnomad4 NFE AF: 0.663

Gnomad4 OTH AF: 0.766

Alfa AF: 0.689 Hom.: 82550

Bravo AF: 0.752

TwinsUK AF: 0.635 AC: 2354

ALSPAC AF: 0.653 AC: 2517

ESP6500AA AF: 0.873 AC: 3846

ESP6500EA AF: 0.660 AC: 5673

ExAC AF: 0.726 AC: 88100

Asia WGS AF: 0.866 AC: 3011 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.060
BayesDel_addAF	Benign	-0.85	T
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.065
DANN	Benign	0.36
DEOGEN2	Benign	0.010	T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.051	N
LIST_S2	Benign	0.043	T
MetaRNN	Benign	0.0000010	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.66	N
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.024
Sift	Benign	0.59	T
Sift4G	Benign	0.63	T
Polyphen		0.0020	B
Vest4		0.036
MPC		0.033
ClinPred		0.0033	T
GERP RS		0.18
Varity_R		0.047
gMVP		0.57

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: rs2846707; hg19: chr11-102576358; COSMIC: COSV99036414;