11-102779693-C-T

Position:

• chr11-102779693-C-T

Variant summary

Our verdict is Benign. Variant got -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. 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 0.10 (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

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:44115): (WTAP pseudogene 1)

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
MMP10	NM_002425.3	c.158G>A	p.Arg53Lys	missense_variant	2/10	ENST00000279441.9	NP_002416.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MMP10	ENST00000279441.9	c.158G>A	p.Arg53Lys	missense_variant	2/10	1	NM_002425.3	ENSP00000279441	P1
WTAPP1	ENST00000371455.7	n.325-18331C>T		intron_variant, non_coding_transcript_variant		4
MMP10	ENST00000539681.1	c.158G>A	p.Arg53Lys	missense_variant	2/4	3		ENSP00000441485

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

GnomAD3 exomes AF: 0.105 AC: 26239 AN: 250846 Hom.: 1918 AF XY: 0.106 AC XY: 14311 AN XY: 135570

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 SAS exome AF: 0.0490

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

Gnomad4 AFR exome AF: 0.0205

Gnomad4 AMR exome AF: 0.0541

Gnomad4 ASJ exome AF: 0.144

Gnomad4 EAS exome AF: 0.000227

Gnomad4 SAS exome AF: 0.0514

Gnomad4 FIN exome AF: 0.146

Gnomad4 NFE exome AF: 0.161

Gnomad4 OTH exome AF: 0.125

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

Gnomad4 AFR AF: 0.0263

Gnomad4 AMR AF: 0.0641

Gnomad4 ASJ AF: 0.144

Gnomad4 EAS AF: 0.00116

Gnomad4 SAS AF: 0.0443

Gnomad4 FIN AF: 0.134

Gnomad4 NFE AF: 0.160

Gnomad4 OTH AF: 0.0832

Alfa AF: 0.137 Hom.: 2337

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;.
MutationTaster	Benign	1.0	N
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

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

Publications

LitVar

Other links and lift over

dbSNP: rs486055; hg19: chr11-102650424; COSMIC: COSV54246499; COSMIC: COSV54246499;