Variant rs652438 details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_002426.6(MMP12):c.1070A>G(p.Asn357Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0603 in 1,611,248 control chromosomes in the GnomAD database, including 4,093 homozygotes. In-silico tool predicts a benign outcome for this variant. 10/14 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 0.097 ( 989 hom., cov: 32)

Exomes 𝑓: 0.057 ( 3104 hom. )

Consequence

MMP12
NM_002426.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.62

Variant links:

Genes affected

MMP12 (HGNC:7158): (matrix metallopeptidase 12) This gene encodes a member of the peptidase M10 family of matrix metalloproteinases (MMPs). Proteins in this 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 protease. This protease degrades soluble and insoluble elastin. This gene may play a role in aneurysm formation and mutations in this gene are associated with lung function and chronic obstructive pulmonary disease (COPD). This gene is part of a cluster of MMP genes on chromosome 11. [provided by RefSeq, Jan 2016]

MMP12 links:

LOC124902741 (HGNC:):

LOC124902741 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=0.0015932322).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.185 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MMP12	NM_002426.6 linkuse as main transcript	c.1070A>G	p.Asn357Ser	missense_variant	8/10	ENST00000571244.3	NP_002417.2
LOC124902741	XR_007062868.1 linkuse as main transcript	n.2705T>C		non_coding_transcript_exon_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MMP12	ENST00000571244.3 linkuse as main transcript	c.1070A>G	p.Asn357Ser	missense_variant	8/10	1	NM_002426.6	ENSP00000458585	P1

Frequencies

GnomAD3 genomes

AF:

0.0971

AC:

14763

AN:

152092

Hom.:

985

Cov.:

show subpopulations

Gnomad AFR

AF:

0.189

Gnomad AMI

AF:

0.116

Gnomad AMR

AF:

0.0696

Gnomad ASJ

AF:

0.127

Gnomad EAS

AF:

0.110

Gnomad SAS

AF:

0.0996

Gnomad FIN

AF:

0.0406

Gnomad MID

AF:

0.161

Gnomad NFE

AF:

0.0527

Gnomad OTH

AF:

0.0977

GnomAD3 exomes

AF:

0.0707

AC:

17522

AN:

247904

Hom.:

878

AF XY:

0.0707

AC XY:

9503

AN XY:

134498

show subpopulations

Gnomad AFR exome

AF:

0.192

Gnomad AMR exome

AF:

0.0411

Gnomad ASJ exome

AF:

0.116

Gnomad EAS exome

AF:

0.126

Gnomad SAS exome

AF:

0.0940

Gnomad FIN exome

AF:

0.0403

Gnomad NFE exome

AF:

0.0495

Gnomad OTH exome

AF:

0.0740

GnomAD4 exome

AF:

0.0565

AC:

82460

AN:

1459038

Hom.:

3104

Cov.:

AF XY:

0.0579

AC XY:

42014

AN XY:

725876

show subpopulations

Gnomad4 AFR exome

AF:

0.195

Gnomad4 AMR exome

AF:

0.0436

Gnomad4 ASJ exome

AF:

0.118

Gnomad4 EAS exome

AF:

0.0843

Gnomad4 SAS exome

AF:

0.0936

Gnomad4 FIN exome

AF:

0.0420

Gnomad4 NFE exome

AF:

0.0469

Gnomad4 OTH exome

AF:

0.0750

GnomAD4 genome

AF:

0.0970

AC:

14769

AN:

152210

Hom.:

989

Cov.:

AF XY:

0.0955

AC XY:

7109

AN XY:

74430

show subpopulations

Gnomad4 AFR

AF:

0.189

Gnomad4 AMR

AF:

0.0694

Gnomad4 ASJ

AF:

0.127

Gnomad4 EAS

AF:

0.110

Gnomad4 SAS

AF:

0.0985

Gnomad4 FIN

AF:

0.0406

Gnomad4 NFE

AF:

0.0527

Gnomad4 OTH

AF:

0.102

Alfa

AF:

0.0608

Hom.:

666

Bravo

AF:

0.103

TwinsUK

AF:

0.0445

AC:

165

ALSPAC

AF:

0.0464

AC:

179

ESP6500AA

AF:

0.181

AC:

648

ESP6500EA

AF:

0.0540

AC:

438

ExAC

AF:

0.0725

AC:

8759

Asia WGS

AF:

0.112

AC:

389

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.086

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.43

CADD

Benign

DANN

Benign

0.68

DEOGEN2

Benign

0.081

FATHMM_MKL

Benign

0.067

LIST_S2

Benign

0.50

MetaRNN

Benign

0.0016

MutationAssessor

Benign

1.5

PrimateAI

Benign

0.28

Sift4G

Uncertain

0.0050

Polyphen

0.20

Vest4

0.15

GERP RS

3.2

Varity_R

0.17

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

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