rs139168339

Variant names:

• chr11-102772905-C-A
• rs139168339
• NM_002425.3:c.1168G>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Moderate BP6_Moderate BS2

The NM_002425.3(MMP10):​c.1168G>T​(p.Ala390Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00223 in 1,613,818 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0014 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0023 (7 hom.)
• Consequence: MMP10 NM_002425.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 7.37
• Publications: 10 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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.082654595).
• BP6: Variant 11-102772905-C-A is Benign according to our data. Variant chr11-102772905-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 2642322.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MMP10	NM_002425.3	c.1168G>T	p.Ala390Ser	missense_variant	Exon 8 of 10	ENST00000279441.9	NP_002416.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MMP10	ENST00000279441.9	c.1168G>T	p.Ala390Ser	missense_variant	Exon 8 of 10	1	NM_002425.3	ENSP00000279441.4
WTAPP1	ENST00000371455.7	n.324+21479C>A		intron_variant	Intron 2 of 4	4
WTAPP1	ENST00000817290.1	n.188+21479C>A		intron_variant	Intron 2 of 4

Frequencies

GnomAD3 genomes AF: 0.00136 AC: 207 AN: 152192 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000410

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000458

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00259

Gnomad OTH AF: 0.00191

GnomAD2 exomes AF: 0.00119 AC: 299 AN: 251162 AF XY: 0.00119

Gnomad AFR exome AF: 0.000493

Gnomad AMR exome AF: 0.000435

Gnomad ASJ exome AF: 0.000596

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000231

Gnomad NFE exome AF: 0.00228

Gnomad OTH exome AF: 0.000979

GnomAD4 exome AF: 0.00232 AC: 3392 AN: 1461508 Hom.: 7 Cov.: 30 AF XY: 0.00227 AC XY: 1648 AN XY: 727056

African (AFR) AF: 0.000418 AC: 14 AN: 33454

American (AMR) AF: 0.000403 AC: 18 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.00107 AC: 28 AN: 26112

East Asian (EAS) AF: 0.00 AC: 0 AN: 39662

South Asian (SAS) AF: 0.00 AC: 0 AN: 86222

European-Finnish (FIN) AF: 0.000243 AC: 13 AN: 53410

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00289 AC: 3210 AN: 1111794

Other (OTH) AF: 0.00181 AC: 109 AN: 60384

GnomAD4 genome AF: 0.00135 AC: 206 AN: 152310 Hom.: 1 Cov.: 32 AF XY: 0.00140 AC XY: 104 AN XY: 74478

African (AFR) AF: 0.000409 AC: 17 AN: 41570

American (AMR) AF: 0.000392 AC: 6 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.000188 AC: 2 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00259 AC: 176 AN: 68032

Other (OTH) AF: 0.00189 AC: 4 AN: 2112

Alfa AF: 0.00219 Hom.: 1

Bravo AF: 0.00144

TwinsUK AF: 0.00216 AC: 8

ALSPAC AF: 0.00285 AC: 11

ESP6500AA AF: 0.000681 AC: 3

ESP6500EA AF: 0.00244 AC: 21

ExAC AF: 0.00113 AC: 137

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00202

EpiControl AF: 0.00267

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Aug 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

MMP10: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.18
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.25	T
Eigen	Pathogenic	0.74
Eigen_PC	Uncertain	0.60
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.037	D
MetaRNN	Benign	0.083	T
MetaSVM	Uncertain	-0.15	T
MutationAssessor	Pathogenic	3.7	H
PhyloP100		7.4
PrimateAI	Benign	0.42	T
PROVEAN	Uncertain	-2.6	D
REVEL	Uncertain	0.41
Sift	Uncertain	0.011	D
Sift4G	Uncertain	0.015	D
Polyphen		1.0	D
Vest4		0.62
MVP		0.72
MPC		0.068
ClinPred		0.26	T
GERP RS		4.5
Varity_R		0.31
gMVP		0.80
Mutation Taster		=72/28	polymorphism

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: rs139168339; hg19: chr11-102643636; COSMIC: COSV108086069; COSMIC: COSV108086069;