11-102779223-A-G

Variant names:

• chr11-102779223-A-G
• rs17860950
• NM_002425.3:c.486T>C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_002425.3(MMP10):​c.486T>C​(p.Phe162Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0658 in 1,612,926 control chromosomes in the GnomAD database, including 4,471 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.097 (1023 hom., cov: 33)
  • Exomes 𝑓: 0.063 (3448 hom.)
• Consequence: MMP10 NM_002425.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.41
• Publications: 9 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BP7: Synonymous conserved (PhyloP=1.41 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.187 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002425.3. 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
	MMP10	NM_002425.3	MANE Select	c.486T>C	p.Phe162Phe	synonymous	Exon 3 of 10	NP_002416.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MMP10	ENST00000279441.9	TSL:1 MANE Select	c.486T>C	p.Phe162Phe	synonymous	Exon 3 of 10	ENSP00000279441.4
	MMP10	ENST00000539681.1	TSL:3	c.486T>C	p.Phe162Phe	synonymous	Exon 3 of 4	ENSP00000441485.1
	WTAPP1	ENST00000371455.7	TSL:4	n.325-18801A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0967 AC: 14710 AN: 152166 Hom.: 1022 Cov.: 33

Gnomad AFR AF: 0.190

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.0897

Gnomad ASJ AF: 0.0858

Gnomad EAS AF: 0.000384

Gnomad SAS AF: 0.0236

Gnomad FIN AF: 0.0342

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0652

Gnomad OTH AF: 0.106

GnomAD2 exomes AF: 0.0612 AC: 15377 AN: 251094 AF XY: 0.0589

Gnomad AFR exome AF: 0.196

Gnomad AMR exome AF: 0.0447

Gnomad ASJ exome AF: 0.0925

Gnomad EAS exome AF: 0.000109

Gnomad FIN exome AF: 0.0354

Gnomad NFE exome AF: 0.0685

Gnomad OTH exome AF: 0.0655

GnomAD4 exome AF: 0.0625 AC: 91321 AN: 1460642 Hom.: 3448 Cov.: 33 AF XY: 0.0614 AC XY: 44616 AN XY: 726668

African (AFR) AF: 0.195 AC: 6514 AN: 33442

American (AMR) AF: 0.0493 AC: 2203 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.0943 AC: 2463 AN: 26126

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39686

South Asian (SAS) AF: 0.0263 AC: 2262 AN: 86168

European-Finnish (FIN) AF: 0.0352 AC: 1880 AN: 53416

Middle Eastern (MID) AF: 0.0964 AC: 474 AN: 4918

European-Non Finnish (NFE) AF: 0.0642 AC: 71386 AN: 1111888

Other (OTH) AF: 0.0686 AC: 4137 AN: 60292

GnomAD4 genome AF: 0.0967 AC: 14732 AN: 152284 Hom.: 1023 Cov.: 33 AF XY: 0.0940 AC XY: 6999 AN XY: 74482

African (AFR) AF: 0.190 AC: 7900 AN: 41516

American (AMR) AF: 0.0896 AC: 1371 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0858 AC: 298 AN: 3472

East Asian (EAS) AF: 0.000385 AC: 2 AN: 5194

South Asian (SAS) AF: 0.0238 AC: 115 AN: 4828

European-Finnish (FIN) AF: 0.0342 AC: 363 AN: 10628

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.0652 AC: 4432 AN: 68026

Other (OTH) AF: 0.104 AC: 220 AN: 2114

Alfa AF: 0.0809 Hom.: 286

Bravo AF: 0.105

Asia WGS AF: 0.0220 AC: 79 AN: 3478

EpiCase AF: 0.0712

EpiControl AF: 0.0699

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	1.0
DANN	Benign	0.55
PhyloP100		1.4
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: rs17860950; hg19: chr11-102649954; COSMIC: COSV54248030; COSMIC: COSV54248030;