Variant rs2499953 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_021801.5(MMP26):c.127A>G(p.Lys43Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0458 in 1,612,874 control chromosomes in the GnomAD database, including 5,990 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 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 0.11 ( 1731 hom., cov: 32)

Exomes 𝑓: 0.039 ( 4259 hom. )

Consequence

MMP26
NM_021801.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.46

Variant links:

Genes affected

MMP26 (HGNC:14249): (matrix metallopeptidase 26) 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. The encoded preproprotein is proteolytically processed to generate the mature enzyme. This enzyme may degrade collagen type IV, fibronectin, fibrinogen, and beta-casein, and activate matrix metalloproteinase-9 by cleavage. The protein differs from most MMP family members in that it lacks a conserved C-terminal protein domain. The encoded protein may promote cell invasion in multiple human cancers. [provided by RefSeq, May 2016]

MMP26 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0045666993).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.286 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MMP26	NM_021801.5 linkuse as main transcript	c.127A>G	p.Lys43Glu	missense_variant	4/8	ENST00000380390.6	NP_068573.2	Q9NRE1
MMP26	NM_001384608.1 linkuse as main transcript	c.-84A>G		5_prime_UTR_variant	4/8		NP_001371537.1
MMP26	XM_011520219.3 linkuse as main transcript	c.-84A>G		5_prime_UTR_variant	3/7		XP_011518521.1	A0A8J8YUH5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
MMP26	ENST00000380390.6 linkuse as main transcript	c.127A>G	p.Lys43Glu	missense_variant	4/8	5	NM_021801.5	ENSP00000369753.1	Q9NRE1
MMP26	ENST00000300762.2 linkuse as main transcript	c.-84A>G		5_prime_UTR_variant	4/8	1		ENSP00000300762.2	A0A8J8YUH5
MMP26	ENST00000690848.1 linkuse as main transcript	c.127A>G	p.Lys43Glu	missense_variant	3/7			ENSP00000510347.1	Q9NRE1

Frequencies

GnomAD3 genomes

AF:

0.108

AC:

16360

AN:

151930

Hom.:

1726

Cov.:

show subpopulations

Gnomad AFR

AF:

0.253

Gnomad AMI

AF:

0.00659

Gnomad AMR

AF:

0.133

Gnomad ASJ

AF:

0.0499

Gnomad EAS

AF:

0.297

Gnomad SAS

AF:

0.0568

Gnomad FIN

AF:

0.0472

Gnomad MID

AF:

0.0506

Gnomad NFE

AF:

0.0176

Gnomad OTH

AF:

0.0934

GnomAD3 exomes

AF:

0.0862

AC:

21497

AN:

249378

Hom.:

2157

AF XY:

0.0747

AC XY:

10077

AN XY:

134866

show subpopulations

Gnomad AFR exome

AF:

0.260

Gnomad AMR exome

AF:

0.193

Gnomad ASJ exome

AF:

0.0476

Gnomad EAS exome

AF:

0.292

Gnomad SAS exome

AF:

0.0459

Gnomad FIN exome

AF:

0.0450

Gnomad NFE exome

AF:

0.0190

Gnomad OTH exome

AF:

0.0604

GnomAD4 exome

AF:

0.0393

AC:

57426

AN:

1460826

Hom.:

4259

Cov.:

AF XY:

0.0381

AC XY:

27673

AN XY:

726742

show subpopulations

Gnomad4 AFR exome

AF:

0.263

Gnomad4 AMR exome

AF:

0.184

Gnomad4 ASJ exome

AF:

0.0491

Gnomad4 EAS exome

AF:

0.278

Gnomad4 SAS exome

AF:

0.0486

Gnomad4 FIN exome

AF:

0.0445

Gnomad4 NFE exome

AF:

0.0156

Gnomad4 OTH exome

AF:

0.0632

GnomAD4 genome

AF:

0.108

AC:

16403

AN:

152048

Hom.:

1731

Cov.:

AF XY:

0.110

AC XY:

8147

AN XY:

74348

show subpopulations

Gnomad4 AFR

AF:

0.253

Gnomad4 AMR

AF:

0.134

Gnomad4 ASJ

AF:

0.0499

Gnomad4 EAS

AF:

0.298

Gnomad4 SAS

AF:

0.0577

Gnomad4 FIN

AF:

0.0472

Gnomad4 NFE

AF:

0.0176

Gnomad4 OTH

AF:

0.0929

Alfa

AF:

0.0406

Hom.:

1038

Bravo

AF:

0.125

TwinsUK

AF:

0.0113

AC:

ALSPAC

AF:

0.0127

AC:

ESP6500AA

AF:

0.245

AC:

1080

ESP6500EA

AF:

0.0218

AC:

187

ExAC

AF:

0.0841

AC:

10205

Asia WGS

AF:

0.162

AC:

562

AN:

3478

EpiCase

AF:

0.0224

EpiControl

AF:

0.0220

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.079

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.62

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0060

T;T

Eigen

Benign

-0.97

Eigen_PC

Benign

-0.97

FATHMM_MKL

Benign

0.039

LIST_S2

Benign

0.42

.;T

MetaRNN

Benign

0.0046

T;T

MetaSVM

Benign

-0.98

MutationAssessor

Uncertain

2.3

M;M

PrimateAI

Benign

0.31

PROVEAN

Benign

-1.0

N;N

REVEL

Benign

0.066

Sift

Benign

0.14

T;T

Sift4G

Benign

0.76

T;T

Polyphen

0.061

B;B

Vest4

0.047

MPC

0.097

ClinPred

0.0047

GERP RS

1.1

Varity_R

0.14

gMVP

0.64

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over