NM_004994.3:c.*3C>T

Variant names:

• chr20-46016371-C-T
• rs20544
• NM_004994.3:c.*3C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_004994.3(MMP9):​c.*3C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.516 in 1,611,636 control chromosomes in the GnomAD database, including 230,116 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.43 (16128 hom., cov: 31)
  • Exomes 𝑓: 0.52 (213988 hom.)
• Consequence: MMP9 NM_004994.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 1.65
• Publications: 54 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BP6: Variant 20-46016371-C-T is Benign according to our data. Variant chr20-46016371-C-T is described in ClinVar as Benign. ClinVar VariationId is 338562.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.571 is higher than 0.05.

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.*3C>T		3_prime_UTR	Exon 13 of 13	NP_004985.2	P14780
	SLC12A5-AS1	NR_147699.1		n.669-1583G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MMP9	ENST00000372330.3	TSL:1 MANE Select	c.*3C>T		3_prime_UTR	Exon 13 of 13	ENSP00000361405.3	P14780
	MMP9	ENST00000898203.1		c.*3C>T		3_prime_UTR	Exon 13 of 13	ENSP00000568262.1
	MMP9	ENST00000898204.1		c.*3C>T		3_prime_UTR	Exon 12 of 12	ENSP00000568263.1

Frequencies

GnomAD3 genomes AF: 0.431 AC: 65522 AN: 151880 Hom.: 16133 Cov.: 31

Gnomad AFR AF: 0.253

Gnomad AMI AF: 0.568

Gnomad AMR AF: 0.388

Gnomad ASJ AF: 0.505

Gnomad EAS AF: 0.00424

Gnomad SAS AF: 0.306

Gnomad FIN AF: 0.480

Gnomad MID AF: 0.579

Gnomad NFE AF: 0.576

Gnomad OTH AF: 0.473

GnomAD2 exomes AF: 0.426 AC: 107143 AN: 251334 AF XY: 0.436

Gnomad AFR exome AF: 0.249

Gnomad AMR exome AF: 0.258

Gnomad ASJ exome AF: 0.507

Gnomad EAS exome AF: 0.00228

Gnomad FIN exome AF: 0.481

Gnomad NFE exome AF: 0.579

Gnomad OTH exome AF: 0.487

GnomAD4 exome AF: 0.525 AC: 766129 AN: 1459638 Hom.: 213988 Cov.: 32 AF XY: 0.521 AC XY: 378490 AN XY: 726260

African (AFR) AF: 0.237 AC: 7929 AN: 33418

American (AMR) AF: 0.270 AC: 12088 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.501 AC: 13092 AN: 26122

East Asian (EAS) AF: 0.00139 AC: 55 AN: 39682

South Asian (SAS) AF: 0.327 AC: 28177 AN: 86210

European-Finnish (FIN) AF: 0.494 AC: 26379 AN: 53398

Middle Eastern (MID) AF: 0.547 AC: 3150 AN: 5760

European-Non Finnish (NFE) AF: 0.581 AC: 645317 AN: 1110044

Other (OTH) AF: 0.497 AC: 29942 AN: 60290

GnomAD4 genome AF: 0.431 AC: 65521 AN: 151998 Hom.: 16128 Cov.: 31 AF XY: 0.420 AC XY: 31243 AN XY: 74322

African (AFR) AF: 0.253 AC: 10487 AN: 41464

American (AMR) AF: 0.388 AC: 5923 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.505 AC: 1752 AN: 3470

East Asian (EAS) AF: 0.00406 AC: 21 AN: 5176

South Asian (SAS) AF: 0.307 AC: 1478 AN: 4816

European-Finnish (FIN) AF: 0.480 AC: 5066 AN: 10550

Middle Eastern (MID) AF: 0.585 AC: 172 AN: 294

European-Non Finnish (NFE) AF: 0.576 AC: 39117 AN: 67932

Other (OTH) AF: 0.468 AC: 987 AN: 2110

Alfa AF: 0.534 Hom.: 34625

Bravo AF: 0.413

Asia WGS AF: 0.158 AC: 556 AN: 3478

EpiCase AF: 0.580

EpiControl AF: 0.582

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	2	Metaphyseal anadysplasia 2 (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	13
DANN	Benign	0.75
PhyloP100		1.6
Mutation Taster		=99/1	polymorphism (auto)

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: rs20544; hg19: chr20-44645010; COSMIC: COSV63434141; COSMIC: COSV63434141;