Genetic Variant MMP23B:p.Leu37Gln (chr1-1632328-T-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_006983.2(MMP23B):c.110T>A(p.Leu37Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000634 in 1,420,654 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 29)

Exomes 𝑓: 0.0000063 ( 0 hom. )

Consequence

MMP23B
NM_006983.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0710

Publications

0 publications found

Variant links:

Genes affected

MMP23B (HGNC:7171): (matrix metallopeptidase 23B) This gene (MMP23B) encodes a member of the matrix metalloproteinase (MMP) family, and it is part of a duplicated region of chromosome 1p36.3. 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. This gene belongs to the more telomeric copy of the duplicated region. [provided by RefSeq, Jul 2008]

MMP23B links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.36586565).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006983.2. 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
	MMP23B	NM_006983.2	MANE Select	c.110T>A	p.Leu37Gln	missense	Exon 1 of 8	NP_008914.1	O75900-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MMP23B	ENST00000356026.10	TSL:1 MANE Select	c.110T>A	p.Leu37Gln	missense	Exon 1 of 8	ENSP00000348308.5	O75900-1
MMP23B	ENST00000378675.7	TSL:1	c.110T>A	p.Leu37Gln	missense	Exon 1 of 7	ENSP00000367945.3	O75086
MMP23B	ENST00000891264.1		c.110T>A	p.Leu37Gln	missense	Exon 1 of 7	ENSP00000561323.1

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

151940

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00

AC:

AN:

43012

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000631

AC:

AN:

1268714

Hom.:

Cov.:

AF XY:

0.00000482

AC XY:

AN XY:

622750

show subpopulations

African (AFR)

AF:

0.0000404

AC:

AN:

24766

American (AMR)

AF:

0.0000534

AC:

AN:

18722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20486

East Asian (EAS)

AF:

0.00

AC:

AN:

27986

South Asian (SAS)

AF:

0.00

AC:

AN:

62596

European-Finnish (FIN)

AF:

0.00

AC:

AN:

30898

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3662

European-Non Finnish (NFE)

AF:

0.00000584

AC:

AN:

1027330

Other (OTH)

AF:

0.00

AC:

AN:

52268

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00000658

AC:

AN:

151940

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74226

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41404

American (AMR)

AF:

0.0000655

AC:

AN:

15258

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5154

South Asian (SAS)

AF:

0.00

AC:

AN:

4796

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10598

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67942

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.097

BayesDel_noAF

Benign

-0.38

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.11

Eigen

Benign

-0.044

Eigen_PC

Benign

-0.17

FATHMM_MKL

Benign

0.48

LIST_S2

Benign

0.55

M_CAP

Pathogenic

0.59

MetaRNN

Benign

0.37

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.0

PhyloP100

0.071

PrimateAI

Pathogenic

0.80

PROVEAN

Benign

-0.96

REVEL

Benign

0.17

Sift

Benign

0.068

Sift4G

Uncertain

0.019

Polyphen

0.99

Vest4

0.22

MutPred

0.65

Gain of catalytic residue at L37 (P = 0.0339)

MVP

0.65

ClinPred

0.41

GERP RS

3.2

PromoterAI

0.013

Neutral

(source)

Varity_R

0.21

gMVP

0.76

Mutation Taster

=87/13

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over