chr11-102842716-G-T

Variant names:

• chr11-102842716-G-T
• rs41380244
• NM_002422.5:c.306C>A

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_Strong BP7 BS2

The NM_002422.5(MMP3):​c.306C>A​(p.Thr102Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000508 in 1,613,866 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. T102T) has been classified as Benign.

• Frequency:
  • Genomes: 𝑓 0.000072 (0 hom., cov: 30)
  • Exomes 𝑓: 0.000049 (0 hom.)
• Consequence: MMP3 NM_002422.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.681

Genes affected

MMP3 (HGNC:7173): (matrix metallopeptidase 3) Proteins of the matrix metalloproteinase (MMP) 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. Most MMP's are secreted as inactive proproteins which are activated when cleaved by extracellular proteinases. This gene encodes an enzyme which degrades fibronectin, laminin, collagens III, IV, IX, and X, and cartilage proteoglycans. The enzyme is thought to be involved in wound repair, progression of atherosclerosis, and tumor initiation. The gene is part of a cluster of MMP genes which localize to chromosome 11q22.3. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP7: Synonymous conserved (PhyloP=-0.681 with no splicing effect.
• BS2: High AC in GnomAd4 at 11 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MMP3	NM_002422.5	c.306C>A	p.Thr102Thr	synonymous_variant	Exon 2 of 10	ENST00000299855.10	NP_002413.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MMP3	ENST00000299855.10	c.306C>A	p.Thr102Thr	synonymous_variant	Exon 2 of 10	1	NM_002422.5	ENSP00000299855.5
MMP3	ENST00000524478.1	n.*148C>A		non_coding_transcript_exon_variant	Exon 2 of 4	4		ENSP00000435255.1
MMP3	ENST00000524478.1	n.*148C>A		3_prime_UTR_variant	Exon 2 of 4	4		ENSP00000435255.1

Frequencies

GnomAD3 genomes AF: 0.0000723 AC: 11 AN: 152064 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0000677 AC: 17 AN: 251098 Hom.: 0 AF XY: 0.0000737 AC XY: 10 AN XY: 135708

Gnomad AFR exome AF: 0.000185

Gnomad AMR exome AF: 0.0000290

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.0000969

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000486 AC: 71 AN: 1461684 Hom.: 0 Cov.: 57 AF XY: 0.0000523 AC XY: 38 AN XY: 727120

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.0000224

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.0000464

Gnomad4 FIN exome AF: 0.0000187

Gnomad4 NFE exome AF: 0.0000540

Gnomad4 OTH exome AF: 0.0000497

GnomAD4 genome AF: 0.0000723 AC: 11 AN: 152182 Hom.: 0 Cov.: 30 AF XY: 0.0000538 AC XY: 4 AN XY: 74384

Gnomad4 AFR AF: 0.0000482

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000579

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000735

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000158 Hom.: 66

EpiCase AF: 0.000109

EpiControl AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.32
DANN	Benign	0.40

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: rs41380244; hg19: chr11-102713447; COSMIC: COSV55407834; COSMIC: COSV55407834;