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

Variant summary

Our verdict is Uncertain significance. Variant got 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

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 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MMP23B	NM_006983.2 link	c.110T>A	p.Leu37Gln	missense_variant	Exon 1 of 8	ENST00000356026.10	NP_008914.1	O75900-1
MMP23B	XM_047432837.1 link	c.110T>A	p.Leu37Gln	missense_variant	Exon 1 of 8		XP_047288793.1
MMP23B	XM_047432838.1 link	c.110T>A	p.Leu37Gln	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.110T>A	p.Leu37Gln	missense_variant	Exon 1 of 8	1	NM_006983.2	ENSP00000348308.5	O75900-1
MMP23B	ENST00000378675.7 link	c.110T>A	p.Leu37Gln	missense_variant	Exon 1 of 7	1		ENSP00000367945.3	O75086
MMP23B	ENST00000472264.1 link	c.110T>A	p.Leu37Gln	missense_variant	Exon 1 of 3	3		ENSP00000424976.1	D6REP6
MMP23B	ENST00000512731.5 link	n.110T>A		non_coding_transcript_exon_variant	Exon 1 of 6	2		ENSP00000423780.1	B4DMZ6

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

GnomAD4 exome

AF:

0.00000631

AC:

AN:

1268714

Hom.:

Cov.:

AF XY:

0.00000482

AC XY:

AN XY:

622750

show subpopulations

Gnomad4 AFR exome

AF:

0.0000404

Gnomad4 AMR exome

AF:

0.0000534

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:

0.00000584

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000658

AC:

AN:

151940

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74226

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 02, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.110T>A (p.L37Q) alteration is located in exon 1 (coding exon 1) of the MMP23B gene. This alteration results from a T to A substitution at nucleotide position 110, causing the leucine (L) at amino acid position 37 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.097

BayesDel_noAF

Benign

-0.38

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.11

T;.;.

Eigen

Benign

-0.044

Eigen_PC

Benign

-0.17

FATHMM_MKL

Benign

0.48

LIST_S2

Benign

0.55

T;T;T

M_CAP

Pathogenic

0.59

MetaRNN

Benign

0.37

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.0

L;.;.

PrimateAI

Pathogenic

0.80

PROVEAN

Benign

-0.96

N;D;N

REVEL

Benign

0.17

Sift

Benign

0.068

T;D;D

Sift4G

Uncertain

0.019

D;D;D

Polyphen

0.99

D;.;D

Vest4

0.22

MutPred

0.65

Gain of catalytic residue at L37 (P = 0.0339);Gain of catalytic residue at L37 (P = 0.0339);Gain of catalytic residue at L37 (P = 0.0339);

MVP

0.65

ClinPred

0.41

GERP RS

3.2

Varity_R

0.21

gMVP

0.76

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