rs17860949

chr11-102779515-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_002425.3(MMP10):c.336C>T(p.His112=) 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

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 -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/exons	MANE	UniProt
MMP10	NM_002425.3	c.336C>T	p.His112=	synonymous_variant	2/10	ENST00000279441.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MMP10	ENST00000279441.9	c.336C>T	p.His112=	synonymous_variant	2/10	1	NM_002425.3	P1
WTAPP1	ENST00000371455.7	n.325-18509G>A		intron_variant, non_coding_transcript_variant		4
MMP10	ENST00000539681.1	c.336C>T	p.His112=	synonymous_variant	2/4	3

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

GnomAD3 exomes AF: 0.114 AC: 28533 AN: 251084 Hom.: 1710 AF XY: 0.117 AC XY: 15903 AN XY: 135708

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 SAS exome AF: 0.137

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

Gnomad4 AFR exome AF: 0.144

Gnomad4 AMR exome AF: 0.0634

Gnomad4 ASJ exome AF: 0.102

Gnomad4 EAS exome AF: 0.0552

Gnomad4 SAS exome AF: 0.140

Gnomad4 FIN exome AF: 0.0977

Gnomad4 NFE exome AF: 0.133

Gnomad4 OTH exome AF: 0.126

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

Gnomad4 AFR AF: 0.140

Gnomad4 AMR AF: 0.0863

Gnomad4 ASJ AF: 0.111

Gnomad4 EAS AF: 0.0775

Gnomad4 SAS AF: 0.138

Gnomad4 FIN AF: 0.0976

Gnomad4 NFE AF: 0.131

Gnomad4 OTH AF: 0.111

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs17860949; hg19: chr11-102650246; COSMIC: COSV54245765; COSMIC: COSV54245765;