1-1632234-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_006983.2(MMP23B):​c.16C>T​(p.Arg6Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000115 in 1,338,228 control chromosomes in the GnomAD database, including 1 homozygotes. 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.00011 ( 1 hom., cov: 29)
Exomes 𝑓: 0.00012 ( 0 hom. )

Consequence

MMP23B
NM_006983.2 missense

Scores

1
18

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.187
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.039727956).
BP6
Variant 1-1632234-C-T is Benign according to our data. Variant chr1-1632234-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3397068.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MMP23BNM_006983.2 linkc.16C>T p.Arg6Cys missense_variant Exon 1 of 8 ENST00000356026.10 NP_008914.1 O75900-1
MMP23BXM_047432837.1 linkc.16C>T p.Arg6Cys missense_variant Exon 1 of 8 XP_047288793.1
MMP23BXM_047432838.1 linkc.16C>T p.Arg6Cys missense_variant Exon 1 of 8 XP_047288794.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MMP23BENST00000356026.10 linkc.16C>T p.Arg6Cys missense_variant Exon 1 of 8 1 NM_006983.2 ENSP00000348308.5 O75900-1
MMP23BENST00000378675.7 linkc.16C>T p.Arg6Cys missense_variant Exon 1 of 7 1 ENSP00000367945.3 O75086
MMP23BENST00000472264.1 linkc.16C>T p.Arg6Cys missense_variant Exon 1 of 3 3 ENSP00000424976.1 D6REP6
MMP23BENST00000512731.5 linkn.16C>T non_coding_transcript_exon_variant Exon 1 of 6 2 ENSP00000423780.1 B4DMZ6

Frequencies

GnomAD3 genomes
AF:
0.000105
AC:
16
AN:
152140
Hom.:
1
Cov.:
29
show subpopulations
Gnomad AFR
AF:
0.000145
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:
0.000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000226
AC:
2
AN:
8838
Hom.:
0
AF XY:
0.000360
AC XY:
2
AN XY:
5556
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000609
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000116
AC:
138
AN:
1186088
Hom.:
0
Cov.:
31
AF XY:
0.000117
AC XY:
67
AN XY:
574426
show subpopulations
Gnomad4 AFR exome
AF:
0.000254
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:
0.000121
Gnomad4 OTH exome
AF:
0.000267
GnomAD4 genome
AF:
0.000105
AC:
16
AN:
152140
Hom.:
1
Cov.:
29
AF XY:
0.000121
AC XY:
9
AN XY:
74330
show subpopulations
Gnomad4 AFR
AF:
0.000145
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:
0.000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000712
Hom.:
0
Bravo
AF:
0.000151

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Aug 27, 2024
Ambry Genetics
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.098
BayesDel_addAF
Benign
-0.40
T
BayesDel_noAF
Benign
-0.45
CADD
Benign
15
DANN
Benign
0.90
DEOGEN2
Benign
0.079
T;.;.
Eigen
Benign
-1.3
Eigen_PC
Benign
-1.3
FATHMM_MKL
Benign
0.0061
N
LIST_S2
Benign
0.51
T;T;T
M_CAP
Benign
0.069
D
MetaRNN
Benign
0.040
T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
-0.90
N;.;.
PrimateAI
Uncertain
0.68
T
PROVEAN
Benign
-0.080
N;D;N
REVEL
Benign
0.094
Sift
Benign
0.27
T;D;T
Sift4G
Benign
0.11
T;D;T
Polyphen
0.0
B;.;B
Vest4
0.046
MutPred
0.37
Loss of MoRF binding (P = 2e-04);Loss of MoRF binding (P = 2e-04);Loss of MoRF binding (P = 2e-04);
MVP
0.11
ClinPred
0.030
T
GERP RS
-2.5
Varity_R
0.048
gMVP
0.30

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.

Other links and lift over

dbSNP: rs906097776; hg19: chr1-1567613; API