20-46013767-G-C

Position:

chr20-46013767-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000372330.3(MMP9):c.1721G>C(p.Arg574Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.927 in 1,613,230 control chromosomes in the GnomAD database, including 697,146 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R574L) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.90 ( 61725 hom., cov: 34)

Exomes 𝑓: 0.93 ( 635421 hom. )

Consequence

MMP9
ENST00000372330.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 0.934

Variant links:

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]

MMP9 links:

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

SLC12A5-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=7.9859115E-7).

BP6

Variant 20-46013767-G-C is Benign according to our data. Variant chr20-46013767-G-C is described in ClinVar as [Benign]. Clinvar id is 282093.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-46013767-G-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.949 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MMP9	NM_004994.3 linkuse as main transcript	c.1721G>C	p.Arg574Pro	missense_variant	10/13	ENST00000372330.3	NP_004985.2
SLC12A5-AS1	NR_147699.1 linkuse as main transcript	n.1690C>G		non_coding_transcript_exon_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MMP9	ENST00000372330.3 linkuse as main transcript	c.1721G>C	p.Arg574Pro	missense_variant	10/13	1	NM_004994.3	ENSP00000361405	P1
SLC12A5-AS1	ENST00000535913.2 linkuse as main transcript	n.1690C>G		non_coding_transcript_exon_variant	3/3	2

Frequencies

GnomAD3 genomes

AF:

0.897

AC:

136526

AN:

152144

Hom.:

61705

Cov.:

show subpopulations

Gnomad AFR

AF:

0.845

Gnomad AMI

AF:

0.991

Gnomad AMR

AF:

0.808

Gnomad ASJ

AF:

0.952

Gnomad EAS

AF:

0.760

Gnomad SAS

AF:

0.859

Gnomad FIN

AF:

0.916

Gnomad MID

AF:

0.949

Gnomad NFE

AF:

0.955

Gnomad OTH

AF:

0.903

GnomAD3 exomes

AF:

0.876

AC:

219719

AN:

250788

Hom.:

98051

AF XY:

0.887

AC XY:

120276

AN XY:

135636

show subpopulations

Gnomad AFR exome

AF:

0.847

Gnomad AMR exome

AF:

0.643

Gnomad ASJ exome

AF:

0.959

Gnomad EAS exome

AF:

0.778

Gnomad SAS exome

AF:

0.860

Gnomad FIN exome

AF:

0.918

Gnomad NFE exome

AF:

0.954

Gnomad OTH exome

AF:

0.907

GnomAD4 exome

AF:

0.930

AC:

1358563

AN:

1460968

Hom.:

635421

Cov.:

AF XY:

0.929

AC XY:

675346

AN XY:

726778

show subpopulations

Gnomad4 AFR exome

AF:

0.842

Gnomad4 AMR exome

AF:

0.663

Gnomad4 ASJ exome

AF:

0.955

Gnomad4 EAS exome

AF:

0.737

Gnomad4 SAS exome

AF:

0.860

Gnomad4 FIN exome

AF:

0.919

Gnomad4 NFE exome

AF:

0.956

Gnomad4 OTH exome

AF:

0.926

GnomAD4 genome

AF:

0.897

AC:

136587

AN:

152262

Hom.:

61725

Cov.:

AF XY:

0.893

AC XY:

66455

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.845

Gnomad4 AMR

AF:

0.808

Gnomad4 ASJ

AF:

0.952

Gnomad4 EAS

AF:

0.759

Gnomad4 SAS

AF:

0.860

Gnomad4 FIN

AF:

0.916

Gnomad4 NFE

AF:

0.955

Gnomad4 OTH

AF:

0.898

Alfa

AF:

0.938

Hom.:

45699

Bravo

AF:

0.884

TwinsUK

AF:

0.959

AC:

3555

ALSPAC

AF:

0.955

AC:

3680

ESP6500AA

AF:

0.855

AC:

3767

ESP6500EA

AF:

0.953

AC:

8198

ExAC

AF:

0.883

AC:

107267

Asia WGS

AF:

0.755

AC:

2626

AN:

3478

EpiCase

AF:

0.955

EpiControl

AF:

0.954

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Metaphyseal anadysplasia 2

Benign:3

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Sep 05, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Apr 27, 2017	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. -
Benign, criteria provided, single submitter	clinical testing	Mendelics	May 28, 2019	- -

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 16, 2018	This variant is associated with the following publications: (PMID: 18512818, 22729913, 19633731, 16574953, 25639450) -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Eurofins Ntd Llc (ga)

Nov 09, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.052

BayesDel_addAF

Benign

-0.79

BayesDel_noAF

Benign

-0.76

CADD

Benign

DANN

Benign

0.75

DEOGEN2

Benign

0.049

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.0044

LIST_S2

Benign

0.093

MetaRNN

Benign

8.0e-7

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-2.5

MutationTaster

Benign

1.0

PrimateAI

Benign

0.35

PROVEAN

Benign

3.9

REVEL

Benign

0.053

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.041

ClinPred

0.012

GERP RS

3.9

Varity_R

0.12

gMVP

0.74

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over