dbSNP rs1168869026: MMP23B:p.Leu36Met (chr1-1632324-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_006983.2(MMP23B):c.106C>A(p.Leu36Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000784 in 1,275,984 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. L36V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 29)

Exomes 𝑓: 7.8e-7 ( 0 hom. )

Consequence

MMP23B
NM_006983.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.336

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 made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.13777503).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MMP23B	NM_006983.2 link	c.106C>A	p.Leu36Met	missense_variant	Exon 1 of 8	ENST00000356026.10	NP_008914.1	O75900-1
MMP23B	XM_047432837.1 link	c.106C>A	p.Leu36Met	missense_variant	Exon 1 of 8		XP_047288793.1
MMP23B	XM_047432838.1 link	c.106C>A	p.Leu36Met	missense_variant	Exon 1 of 8		XP_047288794.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
MMP23B	ENST00000356026.10 link	c.106C>A	p.Leu36Met	missense_variant	Exon 1 of 8	1	NM_006983.2	ENSP00000348308.5	O75900-1
MMP23B	ENST00000378675.7 link	c.106C>A	p.Leu36Met	missense_variant	Exon 1 of 7	1		ENSP00000367945.3	O75086
MMP23B	ENST00000472264.1 link	c.106C>A	p.Leu36Met	missense_variant	Exon 1 of 3	3		ENSP00000424976.1	D6REP6
MMP23B	ENST00000512731.5 link	n.106C>A		non_coding_transcript_exon_variant	Exon 1 of 6	2		ENSP00000423780.1	B4DMZ6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.84e-7

AC:

AN:

1275984

Hom.:

Cov.:

AF XY:

0.00000160

AC XY:

AN XY:

626778

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.70e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Benign

0.93

DEOGEN2

Benign

0.083

T;.;.

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.063

LIST_S2

Benign

0.33

T;T;T

M_CAP

Uncertain

0.21

MetaRNN

Benign

0.14

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.0

L;.;.

PrimateAI

Pathogenic

0.79

PROVEAN

Benign

-0.21

N;N;N

REVEL

Benign

0.059

Sift

Uncertain

0.019

D;D;D

Sift4G

Uncertain

0.016

D;D;D

Polyphen

0.0020

B;.;B

Vest4

0.27

MutPred

0.64

Gain of helix (P = 0.062);Gain of helix (P = 0.062);Gain of helix (P = 0.062);

MVP

0.10

ClinPred

0.099

GERP RS

-3.4

Varity_R

0.078

gMVP

0.53

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over