Genetic Variant MMP23B:p.Gln331* (chr1-1634254-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP6_Moderate

The ENST00000378675.7(MMP23B):c.991C>T(p.Gln331*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: 𝑓 0.000091 ( 1 hom., cov: 10)

Exomes 𝑓: 0.00031 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

MMP23B
ENST00000378675.7 stop_gained

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.75

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.

BP6

Variant 1-1634254-C-T is Benign according to our data. Variant chr1-1634254-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2638049.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MMP23B	NM_006983.2 link	c.924C>T	p.Thr308Thr	synonymous_variant	Exon 7 of 8	ENST00000356026.10	NP_008914.1	O75900-1
MMP23B	XM_047432837.1 link	c.924C>T	p.Thr308Thr	synonymous_variant	Exon 7 of 8		XP_047288793.1
MMP23B	XM_047432838.1 link	c.924C>T	p.Thr308Thr	synonymous_variant	Exon 7 of 8		XP_047288794.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MMP23B	ENST00000356026.10 link	c.924C>T	p.Thr308Thr	synonymous_variant	Exon 7 of 8	1	NM_006983.2	ENSP00000348308.5		O75900-1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

77174

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.000134

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000222

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:

0.0000757

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00655

AC:

349

AN:

53274

Hom.:

AF XY:

0.00723

AC XY:

207

AN XY:

28640

show subpopulations

Gnomad AFR exome

AF:

0.00128

Gnomad AMR exome

AF:

0.00294

Gnomad ASJ exome

AF:

0.00181

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00907

Gnomad FIN exome

AF:

0.00693

Gnomad NFE exome

AF:

0.0107

Gnomad OTH exome

AF:

0.00443

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000308

AC:

152

AN:

493404

Hom.:

Cov.:

AF XY:

0.000361

AC XY:

AN XY:

262920

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000748

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000398

Gnomad4 FIN exome

AF:

0.000241

Gnomad4 NFE exome

AF:

0.000391

Gnomad4 OTH exome

AF:

0.000113

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000907

AC:

AN:

77172

Hom.:

Cov.:

AF XY:

0.000137

AC XY:

AN XY:

36454

show subpopulations

Gnomad4 AFR

AF:

0.000134

Gnomad4 AMR

AF:

0.000222

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000758

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000253

Hom.:

ExAC

AF:

0.00778

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Apr 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

MMP23B: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.56

CADD

Benign

9.6

DANN

Uncertain

0.99

Eigen

Benign

-0.13

Eigen_PC

Benign

-0.19

FATHMM_MKL

Uncertain

0.91

Vest4

0.22

GERP RS

0.43

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