NM_022122.3:c.-23G>T

Variant names:

• chr11-102705737-C-A
• rs11225389
• NM_022122.3:c.-23G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_022122.3(MMP27):​c.-23G>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.237 in 1,545,296 control chromosomes in the GnomAD database, including 47,193 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.18 (3122 hom., cov: 31)
  • Exomes 𝑓: 0.24 (44071 hom.)
• Consequence: MMP27 NM_022122.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0610
• Publications: 17 publications found

Genes affected

MMP27 (HGNC:14250): (matrix metallopeptidase 27) 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. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.251 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022122.3. 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
	MMP27	NM_022122.3	MANE Select	c.-23G>T		5_prime_UTR	Exon 1 of 10	NP_071405.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MMP27	ENST00000260229.5	TSL:1 MANE Select	c.-23G>T		5_prime_UTR	Exon 1 of 10	ENSP00000260229.4

Frequencies

GnomAD3 genomes AF: 0.179 AC: 27141 AN: 151916 Hom.: 3119 Cov.: 31

Gnomad AFR AF: 0.0471

Gnomad AMI AF: 0.229

Gnomad AMR AF: 0.191

Gnomad ASJ AF: 0.179

Gnomad EAS AF: 0.0913

Gnomad SAS AF: 0.149

Gnomad FIN AF: 0.248

Gnomad MID AF: 0.140

Gnomad NFE AF: 0.254

Gnomad OTH AF: 0.161

GnomAD2 exomes AF: 0.209 AC: 48783 AN: 233640 AF XY: 0.210

Gnomad AFR exome AF: 0.0431

Gnomad AMR exome AF: 0.227

Gnomad ASJ exome AF: 0.181

Gnomad EAS exome AF: 0.0961

Gnomad FIN exome AF: 0.261

Gnomad NFE exome AF: 0.247

Gnomad OTH exome AF: 0.194

GnomAD4 exome AF: 0.244 AC: 339509 AN: 1393262 Hom.: 44071 Cov.: 22 AF XY: 0.241 AC XY: 167944 AN XY: 695738

African (AFR) AF: 0.0356 AC: 1111 AN: 31180

American (AMR) AF: 0.217 AC: 8714 AN: 40232

Ashkenazi Jewish (ASJ) AF: 0.177 AC: 4516 AN: 25516

East Asian (EAS) AF: 0.0765 AC: 2946 AN: 38510

South Asian (SAS) AF: 0.166 AC: 13379 AN: 80676

European-Finnish (FIN) AF: 0.267 AC: 14204 AN: 53248

Middle Eastern (MID) AF: 0.124 AC: 699 AN: 5650

European-Non Finnish (NFE) AF: 0.265 AC: 281139 AN: 1060294

Other (OTH) AF: 0.221 AC: 12801 AN: 57956

GnomAD4 genome AF: 0.179 AC: 27140 AN: 152034 Hom.: 3122 Cov.: 31 AF XY: 0.177 AC XY: 13164 AN XY: 74290

African (AFR) AF: 0.0470 AC: 1950 AN: 41478

American (AMR) AF: 0.191 AC: 2911 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.179 AC: 622 AN: 3466

East Asian (EAS) AF: 0.0915 AC: 474 AN: 5178

South Asian (SAS) AF: 0.149 AC: 718 AN: 4814

European-Finnish (FIN) AF: 0.248 AC: 2621 AN: 10550

Middle Eastern (MID) AF: 0.140 AC: 41 AN: 292

European-Non Finnish (NFE) AF: 0.254 AC: 17260 AN: 67964

Other (OTH) AF: 0.159 AC: 335 AN: 2110

Alfa AF: 0.214 Hom.: 12341

Bravo AF: 0.172

Asia WGS AF: 0.106 AC: 370 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.4
DANN	Benign	0.72
PhyloP100		-0.061
PromoterAI		-0.021	Neutral
Mutation Taster		=299/1	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: rs11225389; hg19: chr11-102576468; COSMIC: COSV52780107;