dbSNP rs906097776: MMP23B:p.Arg6Cys (chr1-1632234-C-T) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_006983.2(MMP23B):c.16C>T(p.Arg6Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000115 in 1,338,228 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00011 ( 1 hom., cov: 29)

Exomes 𝑓: 0.00012 ( 0 hom. )

Consequence

MMP23B
NM_006983.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.187

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.039727956).

BP6

Variant 1-1632234-C-T is Benign according to our data. Variant chr1-1632234-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3397068.Status of the report is criteria_provided_single_submitter, 1 stars.

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.16C>T	p.Arg6Cys	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.16C>T	p.Arg6Cys	missense	Exon 1 of 8	ENSP00000348308.5	O75900-1
MMP23B	ENST00000378675.7	TSL:1	c.16C>T	p.Arg6Cys	missense	Exon 1 of 7	ENSP00000367945.3	O75086
MMP23B	ENST00000891264.1		c.16C>T	p.Arg6Cys	missense	Exon 1 of 7	ENSP00000561323.1

Frequencies

GnomAD3 genomes

AF:

0.000105

AC:

AN:

152140

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000226

AC:

AN:

8838

AF XY:

0.000360

show subpopulations

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:

0.000609

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000116

AC:

138

AN:

1186088

Hom.:

Cov.:

AF XY:

0.000117

AC XY:

AN XY:

574426

show subpopulations

African (AFR)

AF:

0.000254

AC:

AN:

23620

American (AMR)

AF:

0.00

AC:

AN:

10220

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

16480

East Asian (EAS)

AF:

0.00

AC:

AN:

27140

South Asian (SAS)

AF:

0.00

AC:

AN:

43608

European-Finnish (FIN)

AF:

0.00

AC:

AN:

28006

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3342

European-Non Finnish (NFE)

AF:

0.000121

AC:

119

AN:

984976

Other (OTH)

AF:

0.000267

AC:

AN:

48696

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

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:

0.000105

AC:

AN:

152140

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74330

show subpopulations

African (AFR)

AF:

0.000145

AC:

AN:

41434

American (AMR)

AF:

0.00

AC:

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.000147

AC:

AN:

67996

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.000151

ClinVar

ClinVar submissions

Significance:Likely benign

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

0.098

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.45

CADD

Benign

(source)

DANN

Benign

0.90

DEOGEN2

Benign

0.079

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.0061

LIST_S2

Benign

0.51

M_CAP

Benign

0.069

MetaRNN

Benign

0.040

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.90

PhyloP100

0.19

PrimateAI

Uncertain

0.68

PROVEAN

Benign

-0.080

REVEL

Benign

0.094

Sift

Benign

0.27

Sift4G

Benign

0.11

Polyphen

0.0

Vest4

0.046

MutPred

0.37

Loss of MoRF binding (P = 2e-04)

MVP

0.11

ClinPred

0.030

GERP RS

-2.5

PromoterAI

0.014

Neutral

(source)

Varity_R

0.048

gMVP

0.30

Mutation Taster

=97/3

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over