chr11-102705627-T-C

Variant names:

• chr11-102705627-T-C
• rs2846707
• NM_022122.3:c.88A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000260229.5(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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.74 (42938 hom., cov: 33)
  • Exomes 𝑓: 0.67 (321569 hom.)
• Consequence: MMP27 ENST00000260229.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.289
• Publications: 39 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000260229.5. 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
	MMP27	NM_022122.3	MANE Select	c.88A>G	p.Met30Val	missense	Exon 1 of 10	NP_071405.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MMP27	ENST00000260229.5	TSL:1 MANE Select	c.88A>G	p.Met30Val	missense	Exon 1 of 10	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

GnomAD2 exomes AF: 0.714 AC: 163364 AN: 228792 AF XY: 0.711

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 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

African (AFR) AF: 0.878 AC: 27138 AN: 30922

American (AMR) AF: 0.726 AC: 28160 AN: 38768

Ashkenazi Jewish (ASJ) AF: 0.684 AC: 17452 AN: 25510

East Asian (EAS) AF: 0.923 AC: 35083 AN: 37992

South Asian (SAS) AF: 0.764 AC: 61298 AN: 80194

European-Finnish (FIN) AF: 0.664 AC: 35339 AN: 53252

Middle Eastern (MID) AF: 0.782 AC: 4429 AN: 5662

European-Non Finnish (NFE) AF: 0.644 AC: 696434 AN: 1080970

Other (OTH) AF: 0.695 AC: 40734 AN: 58596

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

African (AFR) AF: 0.874 AC: 36286 AN: 41508

American (AMR) AF: 0.741 AC: 11318 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.679 AC: 2354 AN: 3468

East Asian (EAS) AF: 0.907 AC: 4697 AN: 5178

South Asian (SAS) AF: 0.789 AC: 3805 AN: 4820

European-Finnish (FIN) AF: 0.678 AC: 7173 AN: 10578

Middle Eastern (MID) AF: 0.779 AC: 229 AN: 294

European-Non Finnish (NFE) AF: 0.663 AC: 45050 AN: 67990

Other (OTH) AF: 0.766 AC: 1618 AN: 2112

Alfa AF: 0.694 Hom.: 110890

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 v4.9

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
PhyloP100		-0.29
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
PromoterAI		0.033	Neutral
Varity_R		0.047
gMVP		0.57
Mutation Taster		=100/0	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: rs2846707; hg19: chr11-102576358; COSMIC: COSV99036414;