11-102775202-A-C

Variant names:

• chr11-102775202-A-C
• rs201248623
• NM_002425.3:c.1052T>G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_002425.3(MMP10):​c.1052T>G​(p.Val351Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000347 in 1,441,100 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000035 (0 hom.)
• Consequence: MMP10 NM_002425.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.13

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 Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.867

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MMP10	NM_002425.3	c.1052T>G	p.Val351Gly	missense_variant	Exon 7 of 10	ENST00000279441.9	NP_002416.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MMP10	ENST00000279441.9	c.1052T>G	p.Val351Gly	missense_variant	Exon 7 of 10	1	NM_002425.3	ENSP00000279441.4
WTAPP1	ENST00000371455.7	n.325-22822A>C		intron_variant	Intron 2 of 4	4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000415 AC: 1 AN: 240914 Hom.: 0 AF XY: 0.00000768 AC XY: 1 AN XY: 130126

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000314

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000347 AC: 5 AN: 1441100 Hom.: 0 Cov.: 30 AF XY: 0.00000140 AC XY: 1 AN XY: 715890

Gnomad4 AFR exome AF: 0.000122

Gnomad4 AMR exome AF: 0.0000237

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.38
BayesDel_addAF	Benign	-0.0021	T
BayesDel_noAF	Benign	-0.14
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.28	T
Eigen	Benign	0.098
Eigen_PC	Benign	-0.18
FATHMM_MKL	Benign	0.26	N
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.0055	T
MetaRNN	Pathogenic	0.87	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Pathogenic	3.7	H
PrimateAI	Benign	0.32	T
PROVEAN	Pathogenic	-6.2	D
REVEL	Benign	0.17
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.58
MutPred		0.72		Loss of stability (P = 0.0094);
MVP		0.51
MPC		0.064
ClinPred		0.98	D
GERP RS		3.1
Varity_R		0.79
gMVP		0.92

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: rs201248623; hg19: chr11-102645933;