rs1430252076

Variant names:

• chr20-46013739-C-A
• rs1430252076
• NM_004994.3:c.1693C>A

Your query was ambiguous. Multiple possible variants found:

• chr20-46013739-C-A
• chr20-46013739-C-G

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_Strong BS2_Supporting

The NM_004994.3(MMP9):​c.1693C>A​(p.Arg565Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000616 in 1,461,486 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R565G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000062 (0 hom.)
• Consequence: MMP9 NM_004994.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.375
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.040578395).
• BS2: High AC in GnomAdExome4 at 9 Unknown,AD gene. Variant has AC lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004994.3. 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
	MMP9	NM_004994.3	MANE Select	c.1693C>A	p.Arg565Ser	missense	Exon 10 of 13	NP_004985.2	P14780
	SLC12A5-AS1	NR_147699.1		n.1718G>T		non_coding_transcript_exon	Exon 3 of 3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MMP9	ENST00000372330.3	TSL:1 MANE Select	c.1693C>A	p.Arg565Ser	missense	Exon 10 of 13	ENSP00000361405.3	P14780
	MMP9	ENST00000898203.1		c.1630C>A	p.Arg544Ser	missense	Exon 10 of 13	ENSP00000568262.1
	MMP9	ENST00000898204.1		c.1564C>A	p.Arg522Ser	missense	Exon 9 of 12	ENSP00000568263.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000616 AC: 9 AN: 1461486 Hom.: 0 Cov.: 35 AF XY: 0.00000550 AC XY: 4 AN XY: 727018

African (AFR) AF: 0.00 AC: 0 AN: 33474

American (AMR) AF: 0.00 AC: 0 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86232

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53396

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5498

European-Non Finnish (NFE) AF: 0.00000809 AC: 9 AN: 1111978

Other (OTH) AF: 0.00 AC: 0 AN: 60354

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	3.2
DANN	Benign	0.82
DEOGEN2	Benign	0.048	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.63	T
M_CAP	Benign	0.0083	T
MetaRNN	Benign	0.041	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-0.43	N
PhyloP100		0.38
PrimateAI	Benign	0.21	T
PROVEAN	Benign	1.3	N
REVEL	Benign	0.073
Sift	Benign	0.74	T
Sift4G	Benign	1.0	T
Polyphen		0.0030	B
Vest4		0.10
MutPred		0.38		Loss of solvent accessibility (P = 0.0606)
MVP		0.28
ClinPred		0.098	T
GERP RS		-2.3
Varity_R		0.35
gMVP		0.49
Mutation Taster		=94/6	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: rs1430252076; hg19: chr20-44642378;