Genetic Variant MMP23B:p.Ala354Gly (chr1-1634513-C-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_006983.2(MMP23B):c.1061C>G(p.Ala354Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 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. A354V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 23)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

MMP23B
NM_006983.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.03

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: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.062779605).

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.1061C>G	p.Ala354Gly	missense	Exon 8 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.1061C>G	p.Ala354Gly	missense	Exon 8 of 8	ENSP00000348308.5	O75900-1
MMP23B	ENST00000378675.7	TSL:1	c.1128C>G	p.Gly376Gly	synonymous	Exon 7 of 7	ENSP00000367945.3	O75086
MMP23B	ENST00000503792.1	TSL:1	c.744C>G	p.Gly248Gly	synonymous	Exon 5 of 5	ENSP00000426857.1	H0YAE5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

981862

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

494420

African (AFR)

AF:

0.00

AC:

AN:

25074

American (AMR)

AF:

0.00

AC:

AN:

32234

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20090

East Asian (EAS)

AF:

0.00

AC:

AN:

33186

South Asian (SAS)

AF:

0.00

AC:

AN:

65364

European-Finnish (FIN)

AF:

0.00

AC:

AN:

44652

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3248

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

714074

Other (OTH)

AF:

0.00

AC:

AN:

43940

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.075

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.69

CADD

Benign

(source)

DANN

Benign

0.58

DEOGEN2

Benign

0.087

Eigen

Benign

-0.74

Eigen_PC

Benign

-0.63

FATHMM_MKL

Benign

0.41

LIST_S2

Benign

0.76

M_CAP

Benign

0.032

MetaRNN

Benign

0.063

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.41

PhyloP100

2.0

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-0.88

REVEL

Benign

0.058

Sift

Benign

0.49

Sift4G

Benign

0.51

Polyphen

0.017

Vest4

0.15

MutPred

0.28

Loss of stability (P = 0.0119)

MVP

0.10

ClinPred

0.18

GERP RS

2.6

Varity_R

0.069

gMVP

0.40

Mutation Taster

=86/14

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over