rs17435959

Positions:

• chr11-102780582-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000279441.9(MMP10):​c.10C>G​(p.Leu4Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0414 in 1,613,382 control chromosomes in the GnomAD database, including 2,113 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.071 (621 hom., cov: 32)
  • Exomes 𝑓: 0.038 (1492 hom.)
• Consequence: MMP10 ENST00000279441.9 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.14

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0014594793).
• BP6: Variant 11-102780582-G-C is Benign according to our data. Variant chr11-102780582-G-C is described in ClinVar as [Benign]. Clinvar id is 1244144.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.156 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MMP10	NM_002425.3	c.10C>G	p.Leu4Val	missense_variant	1/10	ENST00000279441.9	NP_002416.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MMP10	ENST00000279441.9	c.10C>G	p.Leu4Val	missense_variant	1/10	1	NM_002425.3	ENSP00000279441	P1
WTAPP1	ENST00000371455.7	n.325-17442G>C		intron_variant, non_coding_transcript_variant		4
MMP10	ENST00000539681.1	c.10C>G	p.Leu4Val	missense_variant	1/4	3		ENSP00000441485

Frequencies

GnomAD3 genomes AF: 0.0712 AC: 10835 AN: 152116 Hom.: 618 Cov.: 32

Gnomad AFR AF: 0.160

Gnomad AMI AF: 0.0373

Gnomad AMR AF: 0.0423

Gnomad ASJ AF: 0.0199

Gnomad EAS AF: 0.0510

Gnomad SAS AF: 0.0472

Gnomad FIN AF: 0.0565

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0330

Gnomad OTH AF: 0.0617

GnomAD3 exomes AF: 0.0463 AC: 11592 AN: 250474 Hom.: 416 AF XY: 0.0447 AC XY: 6048 AN XY: 135350

Gnomad AFR exome AF: 0.162

Gnomad AMR exome AF: 0.0336

Gnomad ASJ exome AF: 0.0229

Gnomad EAS exome AF: 0.0563

Gnomad SAS exome AF: 0.0495

Gnomad FIN exome AF: 0.0568

Gnomad NFE exome AF: 0.0315

Gnomad OTH exome AF: 0.0393

GnomAD4 exome AF: 0.0383 AC: 55970 AN: 1461148 Hom.: 1492 Cov.: 30 AF XY: 0.0383 AC XY: 27808 AN XY: 726836

Gnomad4 AFR exome AF: 0.166

Gnomad4 AMR exome AF: 0.0361

Gnomad4 ASJ exome AF: 0.0223

Gnomad4 EAS exome AF: 0.0533

Gnomad4 SAS exome AF: 0.0488

Gnomad4 FIN exome AF: 0.0558

Gnomad4 NFE exome AF: 0.0325

Gnomad4 OTH exome AF: 0.0440

GnomAD4 genome AF: 0.0713 AC: 10855 AN: 152234 Hom.: 621 Cov.: 32 AF XY: 0.0711 AC XY: 5289 AN XY: 74430

Gnomad4 AFR AF: 0.160

Gnomad4 AMR AF: 0.0424

Gnomad4 ASJ AF: 0.0199

Gnomad4 EAS AF: 0.0511

Gnomad4 SAS AF: 0.0468

Gnomad4 FIN AF: 0.0565

Gnomad4 NFE AF: 0.0330

Gnomad4 OTH AF: 0.0606

Alfa AF: 0.0378 Hom.: 119

Bravo AF: 0.0748

TwinsUK AF: 0.0345 AC: 128

ALSPAC AF: 0.0317 AC: 122

ESP6500AA AF: 0.154 AC: 678

ESP6500EA AF: 0.0305 AC: 262

ExAC AF: 0.0483 AC: 5864

Asia WGS AF: 0.0630 AC: 219 AN: 3478

EpiCase AF: 0.0309

EpiControl AF: 0.0301

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 24, 2021	This variant is associated with the following publications: (PMID: 26419737) -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	-0.61	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	9.5
DANN	Benign	0.94
DEOGEN2	Benign	0.15	T;T
Eigen	Benign	-0.28
Eigen_PC	Benign	-0.51
FATHMM_MKL	Benign	0.17	N
LIST_S2	Benign	0.41	T;T
MetaRNN	Benign	0.0015	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Pathogenic	2.9	M;.
MutationTaster	Benign	1.0	P
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-1.3	N;N
REVEL	Benign	0.059
Sift	Benign	0.045	D;T
Sift4G	Uncertain	0.055	T;.
Polyphen		0.91	P;.
Vest4		0.074
MPC		0.032
ClinPred		0.026	T
GERP RS		1.6
Varity_R		0.052
gMVP		0.41

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs17435959; hg19: chr11-102651313; COSMIC: COSV54246560; COSMIC: COSV54246560;