rs1939015

Positions:

• chr11-102705644-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_022122.3(MMP27):​c.71C>T​(p.Thr24Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.831 in 1,591,508 control chromosomes in the GnomAD database, including 550,466 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 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 nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.81 (49685 hom., cov: 32)
  • Exomes 𝑓: 0.83 (500781 hom.)
• Consequence: MMP27 NM_022122.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.28

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.2032555E-6).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.841 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MMP27	NM_022122.3	c.71C>T	p.Thr24Met	missense_variant	1/10	ENST00000260229.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MMP27	ENST00000260229.5	c.71C>T	p.Thr24Met	missense_variant	1/10	1	NM_022122.3	P1

Frequencies

GnomAD3 genomes AF: 0.807 AC: 122646 AN: 152052 Hom.: 49668 Cov.: 32

Gnomad AFR AF: 0.734

Gnomad AMI AF: 0.832

Gnomad AMR AF: 0.797

Gnomad ASJ AF: 0.785

Gnomad EAS AF: 0.777

Gnomad SAS AF: 0.778

Gnomad FIN AF: 0.877

Gnomad MID AF: 0.826

Gnomad NFE AF: 0.847

Gnomad OTH AF: 0.804

GnomAD3 exomes AF: 0.817 AC: 192730 AN: 235790 Hom.: 79027 AF XY: 0.817 AC XY: 104263 AN XY: 127652

Gnomad AFR exome AF: 0.726

Gnomad AMR exome AF: 0.800

Gnomad ASJ exome AF: 0.793

Gnomad EAS exome AF: 0.783

Gnomad SAS exome AF: 0.772

Gnomad FIN exome AF: 0.875

Gnomad NFE exome AF: 0.842

Gnomad OTH exome AF: 0.817

GnomAD4 exome AF: 0.833 AC: 1199086 AN: 1439338 Hom.: 500781 Cov.: 34 AF XY: 0.832 AC XY: 595250 AN XY: 715760

Gnomad4 AFR exome AF: 0.727

Gnomad4 AMR exome AF: 0.801

Gnomad4 ASJ exome AF: 0.796

Gnomad4 EAS exome AF: 0.740

Gnomad4 SAS exome AF: 0.779

Gnomad4 FIN exome AF: 0.877

Gnomad4 NFE exome AF: 0.844

Gnomad4 OTH exome AF: 0.823

GnomAD4 genome AF: 0.806 AC: 122708 AN: 152170 Hom.: 49685 Cov.: 32 AF XY: 0.807 AC XY: 60073 AN XY: 74412

Gnomad4 AFR AF: 0.734

Gnomad4 AMR AF: 0.797

Gnomad4 ASJ AF: 0.785

Gnomad4 EAS AF: 0.777

Gnomad4 SAS AF: 0.779

Gnomad4 FIN AF: 0.877

Gnomad4 NFE AF: 0.847

Gnomad4 OTH AF: 0.796

Alfa AF: 0.832 Hom.: 82850

Bravo AF: 0.799

TwinsUK AF: 0.837 AC: 3104

ALSPAC AF: 0.846 AC: 3259

ESP6500AA AF: 0.737 AC: 3246

ESP6500EA AF: 0.835 AC: 7179

ExAC AF: 0.820 AC: 99537

Asia WGS AF: 0.751 AC: 2610 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.069
BayesDel_addAF	Benign	-0.82	T
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.42
DANN	Benign	0.062
DEOGEN2	Benign	0.016	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.0042	N
LIST_S2	Benign	0.20	T
MetaRNN	Benign	0.0000012	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.63	N
MutationTaster	Benign	1.0	P
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.91	N
REVEL	Benign	0.0050
Sift	Benign	0.39	T
Sift4G	Benign	0.34	T
Polyphen		0.0020	B
Vest4		0.013
MPC		0.033
ClinPred		0.0060	T
GERP RS		-2.0
Varity_R		0.014
gMVP		0.43

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: rs1939015; hg19: chr11-102576375; COSMIC: COSV52781018;