rs17860949

Variant names:

• chr11-102779515-G-A
• rs17860949
• NM_002425.3:c.336C>T

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.336C>T​(p.His112His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.127 in 1,613,780 control chromosomes in the GnomAD database, including 13,421 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 0.12 (1197 hom., cov: 33)
  • Exomes 𝑓: 0.13 (12224 hom.)
• Consequence: MMP10 NM_002425.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.758
• Publications: 11 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=-0.8).
• BP7: Synonymous conserved (PhyloP=-0.758 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.137 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MMP10	NM_002425.3	c.336C>T	p.His112His	synonymous_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.336C>T	p.His112His	synonymous_variant	Exon 2 of 10	1	NM_002425.3	ENSP00000279441.4
MMP10	ENST00000539681.1	c.336C>T	p.His112His	synonymous_variant	Exon 2 of 4	3		ENSP00000441485.1
WTAPP1	ENST00000371455.7	n.325-18509G>A		intron_variant	Intron 2 of 4	4
WTAPP1	ENST00000817290.1	n.189-18509G>A		intron_variant	Intron 2 of 4

Frequencies

GnomAD3 genomes AF: 0.125 AC: 18997 AN: 152062 Hom.: 1193 Cov.: 33

Gnomad AFR AF: 0.140

Gnomad AMI AF: 0.227

Gnomad AMR AF: 0.0865

Gnomad ASJ AF: 0.111

Gnomad EAS AF: 0.0773

Gnomad SAS AF: 0.137

Gnomad FIN AF: 0.0976

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.131

Gnomad OTH AF: 0.112

GnomAD2 exomes AF: 0.114 AC: 28533 AN: 251084 AF XY: 0.117

Gnomad AFR exome AF: 0.143

Gnomad AMR exome AF: 0.0594

Gnomad ASJ exome AF: 0.0993

Gnomad EAS exome AF: 0.0822

Gnomad FIN exome AF: 0.0960

Gnomad NFE exome AF: 0.129

Gnomad OTH exome AF: 0.122

GnomAD4 exome AF: 0.127 AC: 185535 AN: 1461600 Hom.: 12224 Cov.: 34 AF XY: 0.127 AC XY: 92678 AN XY: 727112

African (AFR) AF: 0.144 AC: 4825 AN: 33472

American (AMR) AF: 0.0634 AC: 2831 AN: 44644

Ashkenazi Jewish (ASJ) AF: 0.102 AC: 2663 AN: 26128

East Asian (EAS) AF: 0.0552 AC: 2193 AN: 39698

South Asian (SAS) AF: 0.140 AC: 12043 AN: 86252

European-Finnish (FIN) AF: 0.0977 AC: 5217 AN: 53404

Middle Eastern (MID) AF: 0.117 AC: 674 AN: 5768

European-Non Finnish (NFE) AF: 0.133 AC: 147458 AN: 1111852

Other (OTH) AF: 0.126 AC: 7631 AN: 60382

GnomAD4 genome AF: 0.125 AC: 19011 AN: 152180 Hom.: 1197 Cov.: 33 AF XY: 0.122 AC XY: 9046 AN XY: 74420

African (AFR) AF: 0.140 AC: 5802 AN: 41522

American (AMR) AF: 0.0863 AC: 1318 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.111 AC: 385 AN: 3472

East Asian (EAS) AF: 0.0775 AC: 402 AN: 5186

South Asian (SAS) AF: 0.138 AC: 664 AN: 4822

European-Finnish (FIN) AF: 0.0976 AC: 1034 AN: 10596

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

European-Non Finnish (NFE) AF: 0.131 AC: 8937 AN: 67990

Other (OTH) AF: 0.111 AC: 235 AN: 2112

Alfa AF: 0.128 Hom.: 658

Bravo AF: 0.124

Asia WGS AF: 0.109 AC: 380 AN: 3478

EpiCase AF: 0.125

EpiControl AF: 0.132

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	4.5
DANN	Benign	0.68
PhyloP100		-0.76
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: rs17860949; hg19: chr11-102650246; COSMIC: COSV54245765; COSMIC: COSV54245765;