chr12-131840694-G-A

Variant names:

• chr12-131840694-G-A
• rs6598163
• NM_016155.7:c.544G>A

Variant summary

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

The NM_016155.7(MMP17):​c.544G>A​(p.Ala182Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.477 in 1,606,054 control chromosomes in the GnomAD database, including 183,664 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 0.46 (16422 hom., cov: 35)
  • Exomes 𝑓: 0.48 (167242 hom.)
• Consequence: MMP17 NM_016155.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.539
• Publications: 41 publications found

Genes affected

MMP17 (HGNC:7163): (matrix metallopeptidase 17) This gene encodes a member of the peptidase M10 family and membrane-type subfamily of matrix metalloproteinases (MMPs). Proteins in this 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. Members of this subfamily contain a transmembrane domain suggesting that these proteins are expressed at the cell surface rather than secreted. The encoded preproprotein is proteolytically processed to generate the mature protease. This protein is unique among the membrane-type matrix metalloproteinases in that it is anchored to the cell membrane via a glycosylphosphatidylinositol (GPI) anchor. Elevated expression of the encoded protein has been observed in osteoarthritis and multiple human cancers. [provided by RefSeq, Jan 2016]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=4.464984E-4).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.489 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MMP17	NM_016155.7	c.544G>A	p.Ala182Thr	missense_variant	Exon 4 of 10	ENST00000360564.5	NP_057239.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MMP17	ENST00000360564.5	c.544G>A	p.Ala182Thr	missense_variant	Exon 4 of 10	1	NM_016155.7	ENSP00000353767.1

Frequencies

GnomAD3 genomes AF: 0.464 AC: 70584 AN: 152078 Hom.: 16410 Cov.: 35

Gnomad AFR AF: 0.424

Gnomad AMI AF: 0.401

Gnomad AMR AF: 0.459

Gnomad ASJ AF: 0.472

Gnomad EAS AF: 0.505

Gnomad SAS AF: 0.410

Gnomad FIN AF: 0.480

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.488

Gnomad OTH AF: 0.467

GnomAD2 exomes AF: 0.473 AC: 115453 AN: 244164 AF XY: 0.470

Gnomad AFR exome AF: 0.424

Gnomad AMR exome AF: 0.477

Gnomad ASJ exome AF: 0.467

Gnomad EAS exome AF: 0.520

Gnomad FIN exome AF: 0.478

Gnomad NFE exome AF: 0.489

Gnomad OTH exome AF: 0.469

GnomAD4 exome AF: 0.479 AC: 696056 AN: 1453856 Hom.: 167242 Cov.: 81 AF XY: 0.476 AC XY: 344673 AN XY: 723648

African (AFR) AF: 0.432 AC: 14464 AN: 33472

American (AMR) AF: 0.476 AC: 21287 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.476 AC: 12427 AN: 26128

East Asian (EAS) AF: 0.486 AC: 19280 AN: 39692

South Asian (SAS) AF: 0.405 AC: 34926 AN: 86258

European-Finnish (FIN) AF: 0.489 AC: 22308 AN: 45600

Middle Eastern (MID) AF: 0.439 AC: 2530 AN: 5768

European-Non Finnish (NFE) AF: 0.486 AC: 540765 AN: 1111882

Other (OTH) AF: 0.465 AC: 28069 AN: 60336

GnomAD4 genome AF: 0.464 AC: 70631 AN: 152198 Hom.: 16422 Cov.: 35 AF XY: 0.460 AC XY: 34241 AN XY: 74404

African (AFR) AF: 0.424 AC: 17617 AN: 41542

American (AMR) AF: 0.459 AC: 7027 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.472 AC: 1639 AN: 3472

East Asian (EAS) AF: 0.505 AC: 2612 AN: 5168

South Asian (SAS) AF: 0.409 AC: 1976 AN: 4828

European-Finnish (FIN) AF: 0.480 AC: 5091 AN: 10600

Middle Eastern (MID) AF: 0.398 AC: 117 AN: 294

European-Non Finnish (NFE) AF: 0.489 AC: 33206 AN: 67974

Other (OTH) AF: 0.464 AC: 980 AN: 2112

Alfa AF: 0.484 Hom.: 52275

Bravo AF: 0.462

TwinsUK AF: 0.481 AC: 1785

ALSPAC AF: 0.488 AC: 1880

ESP6500AA AF: 0.436 AC: 1919

ESP6500EA AF: 0.490 AC: 4217

ExAC AF: 0.472 AC: 57269

Asia WGS AF: 0.456 AC: 1591 AN: 3478

EpiCase AF: 0.485

EpiControl AF: 0.483

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.063
BayesDel_addAF	Benign	-0.72	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	0.0010
DANN	Benign	0.96
DEOGEN2	Benign	0.024	T;.;.;.;T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.082	N
LIST_S2	Benign	0.068	T;T;T;T;T
MetaRNN	Benign	0.00045	T;T;T;T;T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	-0.050	N;.;.;.;.
PhyloP100		-0.54
PrimateAI	Benign	0.30	T
PROVEAN	Benign	0.45	N;N;N;N;N
REVEL	Benign	0.020
Sift	Benign	0.20	T;T;T;T;T
Sift4G	Benign	0.52	T;T;T;T;T
Polyphen		0.051	B;.;.;.;.
Vest4		0.039
MPC		0.20
ClinPred		0.012	T
GERP RS		-5.1
Varity_R		0.019
gMVP		0.27
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: rs6598163; hg19: chr12-132325239; COSMIC: COSV62178537; COSMIC: COSV62178537;