11-102779693-C-T

Variant names:

• chr11-102779693-C-T
• rs486055
• NM_002425.3:c.158G>A

Variant summary

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

The NM_002425.3(MMP10):​c.158G>A​(p.Arg53Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.137 in 1,613,764 control chromosomes in the GnomAD database, including 17,222 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 0.10 (1112 hom., cov: 33)
  • Exomes 𝑓: 0.14 (16110 hom.)
• Consequence: MMP10 NM_002425.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.250
• Publications: 50 publications found

Genes affected

MMP10 (HGNC:7156): (matrix metallopeptidase 10) This gene encodes a member of the peptidase M10 family 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. The encoded preproprotein is proteolytically processed to generate the mature protease. This secreted protease breaks down fibronectin, laminin, elastin, proteoglycan core protein, gelatins, and several types of collagen. The gene is part of a cluster of MMP genes on chromosome 11. [provided by RefSeq, Jan 2016]

WTAPP1 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.0017623305).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.158 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MMP10	NM_002425.3	c.158G>A	p.Arg53Lys	missense_variant	Exon 2 of 10	ENST00000279441.9	NP_002416.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MMP10	ENST00000279441.9	c.158G>A	p.Arg53Lys	missense_variant	Exon 2 of 10	1	NM_002425.3	ENSP00000279441.4
MMP10	ENST00000539681.1	c.158G>A	p.Arg53Lys	missense_variant	Exon 2 of 4	3		ENSP00000441485.1
WTAPP1	ENST00000371455.7	n.325-18331C>T		intron_variant	Intron 2 of 4	4
WTAPP1	ENST00000817290.1	n.189-18331C>T		intron_variant	Intron 2 of 4

Frequencies

GnomAD3 genomes AF: 0.101 AC: 15431 AN: 152068 Hom.: 1112 Cov.: 33

Gnomad AFR AF: 0.0264

Gnomad AMI AF: 0.134

Gnomad AMR AF: 0.0641

Gnomad ASJ AF: 0.144

Gnomad EAS AF: 0.00116

Gnomad SAS AF: 0.0437

Gnomad FIN AF: 0.134

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.160

Gnomad OTH AF: 0.0836

GnomAD2 exomes AF: 0.105 AC: 26239 AN: 250846 AF XY: 0.106

Gnomad AFR exome AF: 0.0238

Gnomad AMR exome AF: 0.0517

Gnomad ASJ exome AF: 0.145

Gnomad EAS exome AF: 0.000381

Gnomad FIN exome AF: 0.142

Gnomad NFE exome AF: 0.153

Gnomad OTH exome AF: 0.113

GnomAD4 exome AF: 0.141 AC: 205770 AN: 1461578 Hom.: 16110 Cov.: 34 AF XY: 0.139 AC XY: 100932 AN XY: 727082

African (AFR) AF: 0.0205 AC: 685 AN: 33466

American (AMR) AF: 0.0541 AC: 2414 AN: 44640

Ashkenazi Jewish (ASJ) AF: 0.144 AC: 3768 AN: 26130

East Asian (EAS) AF: 0.000227 AC: 9 AN: 39700

South Asian (SAS) AF: 0.0514 AC: 4432 AN: 86250

European-Finnish (FIN) AF: 0.146 AC: 7823 AN: 53400

Middle Eastern (MID) AF: 0.0659 AC: 380 AN: 5768

European-Non Finnish (NFE) AF: 0.161 AC: 178701 AN: 1111840

Other (OTH) AF: 0.125 AC: 7558 AN: 60384

GnomAD4 genome AF: 0.101 AC: 15432 AN: 152186 Hom.: 1112 Cov.: 33 AF XY: 0.0974 AC XY: 7244 AN XY: 74406

African (AFR) AF: 0.0263 AC: 1094 AN: 41522

American (AMR) AF: 0.0641 AC: 979 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.144 AC: 501 AN: 3470

East Asian (EAS) AF: 0.00116 AC: 6 AN: 5178

South Asian (SAS) AF: 0.0443 AC: 214 AN: 4828

European-Finnish (FIN) AF: 0.134 AC: 1416 AN: 10582

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.160 AC: 10905 AN: 68000

Other (OTH) AF: 0.0832 AC: 176 AN: 2116

Alfa AF: 0.132 Hom.: 2762

Bravo AF: 0.0927

TwinsUK AF: 0.155 AC: 573

ALSPAC AF: 0.161 AC: 622

ESP6500AA AF: 0.0272 AC: 120

ESP6500EA AF: 0.156 AC: 1343

ExAC AF: 0.105 AC: 12782

Asia WGS AF: 0.0150 AC: 53 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_addAF	Benign	-0.66	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	13
DANN	Benign	0.80
DEOGEN2	Benign	0.049	T;T
Eigen	Benign	-0.76
Eigen_PC	Benign	-0.65
FATHMM_MKL	Benign	0.31	N
LIST_S2	Benign	0.28	T;T
MetaRNN	Benign	0.0018	T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.74	N;.
PhyloP100		0.25
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.38	N;N
REVEL	Benign	0.070
Sift	Benign	0.40	T;T
Sift4G	Benign	0.80	T;.
Polyphen		0.033	B;.
Vest4		0.037
MPC		0.011
ClinPred		0.0047	T
GERP RS		4.3
Varity_R		0.16
gMVP		0.30
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs486055; hg19: chr11-102650424; COSMIC: COSV54246499; COSMIC: COSV54246499;