11-102779658-C-T

Variant names:

• chr11-102779658-C-T
• rs17293607
• NM_002425.3:c.193G>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.193G>A​(p.Gly65Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.13 in 1,613,726 control chromosomes in the GnomAD database, including 15,045 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 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 (1076 hom., cov: 32)
  • Exomes 𝑓: 0.13 (13969 hom.)
• Consequence: MMP10 NM_002425.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.08
• Publications: 30 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=0.0020132065).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.138 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MMP10	NM_002425.3	c.193G>A	p.Gly65Arg	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.193G>A	p.Gly65Arg	missense_variant	Exon 2 of 10	1	NM_002425.3	ENSP00000279441.4
MMP10	ENST00000539681.1	c.193G>A	p.Gly65Arg	missense_variant	Exon 2 of 4	3		ENSP00000441485.1
WTAPP1	ENST00000371455.7	n.325-18366C>T		intron_variant	Intron 2 of 4	4
WTAPP1	ENST00000817290.1	n.189-18366C>T		intron_variant	Intron 2 of 4

Frequencies

GnomAD3 genomes AF: 0.105 AC: 15949 AN: 152010 Hom.: 1075 Cov.: 32

Gnomad AFR AF: 0.0325

Gnomad AMI AF: 0.0899

Gnomad AMR AF: 0.101

Gnomad ASJ AF: 0.130

Gnomad EAS AF: 0.0189

Gnomad SAS AF: 0.0698

Gnomad FIN AF: 0.209

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.141

Gnomad OTH AF: 0.124

GnomAD2 exomes AF: 0.115 AC: 28787 AN: 250966 AF XY: 0.118

Gnomad AFR exome AF: 0.0303

Gnomad AMR exome AF: 0.0722

Gnomad ASJ exome AF: 0.140

Gnomad EAS exome AF: 0.00751

Gnomad FIN exome AF: 0.198

Gnomad NFE exome AF: 0.147

Gnomad OTH exome AF: 0.147

GnomAD4 exome AF: 0.132 AC: 193555 AN: 1461596 Hom.: 13969 Cov.: 35 AF XY: 0.131 AC XY: 95519 AN XY: 727078

African (AFR) AF: 0.0295 AC: 986 AN: 33470

American (AMR) AF: 0.0750 AC: 3348 AN: 44628

Ashkenazi Jewish (ASJ) AF: 0.139 AC: 3625 AN: 26132

East Asian (EAS) AF: 0.0436 AC: 1732 AN: 39700

South Asian (SAS) AF: 0.0777 AC: 6702 AN: 86252

European-Finnish (FIN) AF: 0.193 AC: 10282 AN: 53394

Middle Eastern (MID) AF: 0.166 AC: 957 AN: 5768

European-Non Finnish (NFE) AF: 0.142 AC: 158331 AN: 1111870

Other (OTH) AF: 0.126 AC: 7592 AN: 60382

GnomAD4 genome AF: 0.105 AC: 15941 AN: 152130 Hom.: 1076 Cov.: 32 AF XY: 0.107 AC XY: 7959 AN XY: 74356

African (AFR) AF: 0.0324 AC: 1345 AN: 41538

American (AMR) AF: 0.100 AC: 1534 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.130 AC: 450 AN: 3468

East Asian (EAS) AF: 0.0190 AC: 98 AN: 5160

South Asian (SAS) AF: 0.0691 AC: 333 AN: 4822

European-Finnish (FIN) AF: 0.209 AC: 2206 AN: 10556

Middle Eastern (MID) AF: 0.229 AC: 67 AN: 292

European-Non Finnish (NFE) AF: 0.141 AC: 9569 AN: 67986

Other (OTH) AF: 0.122 AC: 257 AN: 2114

Alfa AF: 0.128 Hom.: 5734

Bravo AF: 0.0949

TwinsUK AF: 0.139 AC: 516

ALSPAC AF: 0.136 AC: 525

ESP6500AA AF: 0.0315 AC: 139

ESP6500EA AF: 0.145 AC: 1250

ExAC AF: 0.115 AC: 13979

Asia WGS AF: 0.0450 AC: 156 AN: 3478

EpiCase AF: 0.148

EpiControl AF: 0.154

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.58	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	17
DANN	Uncertain	0.98
DEOGEN2	Benign	0.047	T;T
Eigen	Benign	-0.68
Eigen_PC	Benign	-0.54
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Benign	0.16	T;T
MetaRNN	Benign	0.0020	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.43	N;.
PhyloP100		1.1
PrimateAI	Benign	0.33	T
PROVEAN	Benign	2.0	N;N
REVEL	Benign	0.090
Sift	Uncertain	0.020	D;D
Sift4G	Uncertain	0.027	D;.
Polyphen		0.015	B;.
Vest4		0.046
MutPred		0.15		Gain of MoRF binding (P = 0.0188);Gain of MoRF binding (P = 0.0188);
MPC		0.011
ClinPred		0.015	T
GERP RS		3.3
Varity_R		0.16
gMVP		0.53
Mutation Taster		=92/8	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: rs17293607; hg19: chr11-102650389; COSMIC: COSV54245905; COSMIC: COSV54245905;