Genetic Variant MMP23B:p.Val388Leu (chr1-1634614-G-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_006983.2(MMP23B):c.1162G>C(p.Val388Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 24)

Exomes 𝑓: 0.000077 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

MMP23B
NM_006983.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.22

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 made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.077718854).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MMP23B	NM_006983.2 link	c.1162G>C	p.Val388Leu	missense_variant	Exon 8 of 8	ENST00000356026.10	NP_008914.1	O75900-1
MMP23B	XM_047432837.1 link	c.1159G>C	p.Val387Leu	missense_variant	Exon 8 of 8		XP_047288793.1
MMP23B	XM_047432838.1 link	c.*167G>C		3_prime_UTR_variant	Exon 8 of 8		XP_047288794.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MMP23B	ENST00000356026.10 link	c.1162G>C	p.Val388Leu	missense_variant	Exon 8 of 8	1	NM_006983.2	ENSP00000348308.5		O75900-1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

150512

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.0000485

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:

0.0000889

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000770

AC:

AN:

831124

Hom.:

Cov.:

AF XY:

0.0000666

AC XY:

AN XY:

420226

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:

0.000105

Gnomad4 OTH exome

AF:

0.0000259

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000531

AC:

AN:

150632

Hom.:

Cov.:

AF XY:

0.0000545

AC XY:

AN XY:

73446

show subpopulations

Gnomad4 AFR

AF:

0.0000483

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000890

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000843

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Nov 15, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1162G>C (p.V388L) alteration is located in exon 8 (coding exon 8) of the MMP23B gene. This alteration results from a G to C substitution at nucleotide position 1162, causing the valine (V) at amino acid position 388 to be replaced by a leucine (L). 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

-0.30

BayesDel_noAF

Benign

-0.67

CADD

Benign

DANN

Benign

0.54

DEOGEN2

Benign

0.065

Eigen

Benign

-0.82

Eigen_PC

Benign

-0.73

FATHMM_MKL

Benign

0.69

LIST_S2

Benign

0.74

M_CAP

Benign

0.019

MetaRNN

Benign

0.078

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.080

PrimateAI

Uncertain

0.73

PROVEAN

Benign

-0.52

REVEL

Benign

0.034

Sift

Benign

0.36

Sift4G

Benign

0.84

Polyphen

0.0050

Vest4

0.15

MutPred

0.16

Loss of methylation at R389 (P = 0.1425);

MVP

0.15

ClinPred

0.064

GERP RS

2.7

Varity_R

0.047

gMVP

0.65

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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