Variant rs61754773 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_002424.3(MMP8):c.898G>A(p.Asp300Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000233 in 1,564,942 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00019 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00024 ( 3 hom. )

Consequence

MMP8
NM_002424.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.38

Variant links:

Genes affected

MMP8 (HGNC:7175): (matrix metallopeptidase 8) This gene encodes a member of the matrix metalloproteinase (MMP) family of proteins. These proteins are involved in the breakdown of extracellular matrix in embryonic development, reproduction, and tissue remodeling, as well as in disease processes, such as arthritis and metastasis. Proteolysis at different sites on this protein results in multiple active forms of the enzyme with distinct N-termini. This protein functions in the degradation of type I, II and III collagens. The gene is part of a cluster of MMP genes which localize to chromosome 11q22.3. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2015]

MMP8 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009745091).

BP6

Variant 11-102716306-C-T is Benign according to our data. Variant chr11-102716306-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 742574.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MMP8	NM_002424.3 link	c.898G>A	p.Asp300Asn	missense_variant	Exon 6 of 10	ENST00000236826.8	NP_002415.1	P22894

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
MMP8	ENST00000236826.8 link	c.898G>A	p.Asp300Asn	missense_variant	Exon 6 of 10	1	NM_002424.3	ENSP00000236826.3	P22894
MMP8	ENST00000438475.2 link	c.823G>A	p.Asp275Asn	missense_variant	Exon 6 of 9	5		ENSP00000401004.2	H7C1M3
MMP8	ENST00000528662.6 link	n.*875G>A		non_coding_transcript_exon_variant	Exon 8 of 12	5		ENSP00000431431.2	E9PL87
MMP8	ENST00000528662.6 link	n.*875G>A		3_prime_UTR_variant	Exon 8 of 12	5		ENSP00000431431.2	E9PL87

Frequencies

GnomAD3 genomes

AF:

0.000194

AC:

AN:

149504

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000148

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000679

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00218

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000148

Gnomad OTH

AF:

0.000485

GnomAD3 exomes

AF:

0.000290

AC:

AN:

241792

Hom.:

AF XY:

0.000283

AC XY:

AN XY:

130602

show subpopulations

Gnomad AFR exome

AF:

0.000313

Gnomad AMR exome

AF:

0.0000927

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00325

Gnomad SAS exome

AF:

0.0000354

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000682

GnomAD4 exome

AF:

0.000237

AC:

336

AN:

1415324

Hom.:

Cov.:

AF XY:

0.000231

AC XY:

163

AN XY:

704936

show subpopulations

Gnomad4 AFR exome

AF:

0.0000946

Gnomad4 AMR exome

AF:

0.0000954

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00795

Gnomad4 SAS exome

AF:

0.0000120

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000120

Gnomad4 OTH exome

AF:

0.000241

GnomAD4 genome

AF:

0.000187

AC:

AN:

149618

Hom.:

Cov.:

AF XY:

0.000165

AC XY:

AN XY:

72764

show subpopulations

Gnomad4 AFR

AF:

0.000147

Gnomad4 AMR

AF:

0.000611

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00219

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000148

Gnomad4 OTH

AF:

0.000480

Alfa

AF:

0.000109

Hom.:

ExAC

AF:

0.000288

AC:

Asia WGS

AF:

0.00231

AC:

AN:

3478

EpiCase

AF:

0.0000550

EpiControl

AF:

0.0000600

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jun 13, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.59

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.12

Eigen

Benign

-0.043

Eigen_PC

Benign

-0.051

FATHMM_MKL

Benign

0.72

LIST_S2

Benign

0.85

M_CAP

Benign

0.0079

MetaRNN

Benign

0.0097

MetaSVM

Benign

-0.92

MutationAssessor

Benign

1.7

PrimateAI

Benign

0.47

PROVEAN

Uncertain

-3.3

REVEL

Benign

0.050

Sift

Benign

0.12

Sift4G

Benign

0.18

Polyphen

0.0070

Vest4

0.30

MVP

0.53

MPC

0.049

ClinPred

0.040

GERP RS

3.0

Varity_R

0.099

gMVP

0.47

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over