rs13925

Variant names:

• chr20-46016326-G-A
• rs13925
• NM_004994.3:c.2082G>A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_004994.3(MMP9):​c.2082G>A​(p.Val694Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.148 in 1,613,864 control chromosomes in the GnomAD database, including 18,445 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.15 (1672 hom., cov: 32)
  • Exomes 𝑓: 0.15 (16773 hom.)
• Consequence: MMP9 NM_004994.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 1.58

Genes affected

MMP9 (HGNC:7176): (matrix metallopeptidase 9) 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. The enzyme encoded by this gene degrades type IV and V collagens. Studies in rhesus monkeys suggest that the enzyme is involved in IL-8-induced mobilization of hematopoietic progenitor cells from bone marrow, and murine studies suggest a role in tumor-associated tissue remodeling. [provided by RefSeq, Jul 2008]

SLC12A5-AS1 (HGNC:53143): (SLC12A5 and MMP9 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BP6: Variant 20-46016326-G-A is Benign according to our data. Variant chr20-46016326-G-A is described in ClinVar as [Benign]. Clinvar id is 338561.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.58 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.223 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MMP9	NM_004994.3	c.2082G>A	p.Val694Val	synonymous_variant	Exon 13 of 13	ENST00000372330.3	NP_004985.2
SLC12A5-AS1	NR_147699.1	n.669-1538C>T		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MMP9	ENST00000372330.3	c.2082G>A	p.Val694Val	synonymous_variant	Exon 13 of 13	1	NM_004994.3	ENSP00000361405.3
SLC12A5-AS1	ENST00000535913.2	n.669-1538C>T		intron_variant	Intron 2 of 2	2

Frequencies

GnomAD3 genomes AF: 0.146 AC: 22200 AN: 152014 Hom.: 1672 Cov.: 32

Gnomad AFR AF: 0.147

Gnomad AMI AF: 0.0791

Gnomad AMR AF: 0.0919

Gnomad ASJ AF: 0.157

Gnomad EAS AF: 0.148

Gnomad SAS AF: 0.235

Gnomad FIN AF: 0.170

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.148

Gnomad OTH AF: 0.144

GnomAD3 exomes AF: 0.146 AC: 36588 AN: 251428 Hom.: 2931 AF XY: 0.153 AC XY: 20764 AN XY: 135896

Gnomad AFR exome AF: 0.144

Gnomad AMR exome AF: 0.0637

Gnomad ASJ exome AF: 0.159

Gnomad EAS exome AF: 0.131

Gnomad SAS exome AF: 0.237

Gnomad FIN exome AF: 0.169

Gnomad NFE exome AF: 0.142

Gnomad OTH exome AF: 0.151

GnomAD4 exome AF: 0.148 AC: 216641 AN: 1461732 Hom.: 16773 Cov.: 34 AF XY: 0.151 AC XY: 110164 AN XY: 727182

Gnomad4 AFR exome AF: 0.147

Gnomad4 AMR exome AF: 0.0685

Gnomad4 ASJ exome AF: 0.159

Gnomad4 EAS exome AF: 0.162

Gnomad4 SAS exome AF: 0.233

Gnomad4 FIN exome AF: 0.165

Gnomad4 NFE exome AF: 0.143

Gnomad4 OTH exome AF: 0.157

GnomAD4 genome AF: 0.146 AC: 22213 AN: 152132 Hom.: 1672 Cov.: 32 AF XY: 0.146 AC XY: 10894 AN XY: 74376

Gnomad4 AFR AF: 0.147

Gnomad4 AMR AF: 0.0916

Gnomad4 ASJ AF: 0.157

Gnomad4 EAS AF: 0.148

Gnomad4 SAS AF: 0.234

Gnomad4 FIN AF: 0.170

Gnomad4 NFE AF: 0.148

Gnomad4 OTH AF: 0.148

Alfa AF: 0.141 Hom.: 3014

Bravo AF: 0.139

Asia WGS AF: 0.181 AC: 628 AN: 3478

EpiCase AF: 0.148

EpiControl AF: 0.141

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Metaphyseal anadysplasia 2 Benign:2

Sep 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	8.2
DANN	Benign	0.76

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: rs13925; hg19: chr20-44644965; COSMIC: COSV63433827; COSMIC: COSV63433827;