rs901024960

Variant names:

• chr11-102772013-A-C
• rs901024960
• NM_002425.3:c.1329T>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_002425.3(MMP10):​c.1329T>G​(p.Phe443Leu) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/24 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MMP10 NM_002425.3 missense, splice_region
• Scores: Splicing: ADA: 0.0001519
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.895
• Publications: 0 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.27273875).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MMP10	NM_002425.3	MANE Select	c.1329T>G	p.Phe443Leu	missense splice_region	Exon 9 of 10	NP_002416.1	P09238

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MMP10	ENST00000279441.9	TSL:1 MANE Select	c.1329T>G	p.Phe443Leu	missense splice_region	Exon 9 of 10	ENSP00000279441.4	P09238
	WTAPP1	ENST00000371455.7	TSL:4	n.324+20587A>C		intron	N/A
	WTAPP1	ENST00000817290.1		n.188+20587A>C		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.74
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	18
DANN	Benign	0.96
DEOGEN2	Benign	0.065	T
Eigen	Benign	-0.16
Eigen_PC	Benign	-0.25
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.68	T
M_CAP	Benign	0.0048	T
MetaRNN	Benign	0.27	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		0.90
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.083
Sift	Benign	0.24	T
Sift4G	Benign	0.27	T
Polyphen		0.91	P
Vest4		0.31
MutPred		0.52		Loss of sheet (P = 0.1398)
MVP		0.42
MPC		0.024
ClinPred		0.69	D
GERP RS		2.9
Varity_R		0.072
gMVP		0.44
Mutation Taster		=85/15	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00015
dbscSNV1_RF	Benign	0.076
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: rs901024960; hg19: chr11-102642744;