Genetic Variant NM_006983.2:c.44G>T (chr1-1632262-G-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_006983.2(MMP23B):c.44G>T(p.Gly15Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000164 in 1,218,592 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 29)

Exomes 𝑓: 0.0000016 ( 0 hom. )

Consequence

MMP23B
NM_006983.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -3.07

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.08750388).

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.44G>T	p.Gly15Val	missense	Exon 1 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.44G>T	p.Gly15Val	missense	Exon 1 of 8	ENSP00000348308.5	O75900-1
MMP23B	ENST00000378675.7	TSL:1	c.44G>T	p.Gly15Val	missense	Exon 1 of 7	ENSP00000367945.3	O75086
MMP23B	ENST00000891264.1		c.44G>T	p.Gly15Val	missense	Exon 1 of 7	ENSP00000561323.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000164

AC:

AN:

1218592

Hom.:

Cov.:

AF XY:

0.00000168

AC XY:

AN XY:

593926

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

24320

American (AMR)

AF:

0.00

AC:

AN:

14030

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18572

East Asian (EAS)

AF:

0.00

AC:

AN:

27336

South Asian (SAS)

AF:

0.0000393

AC:

AN:

50934

European-Finnish (FIN)

AF:

0.00

AC:

AN:

29556

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3520

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1000184

Other (OTH)

AF:

0.00

AC:

AN:

50140

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.077

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.46

CADD

Benign

9.8

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.088

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.062

LIST_S2

Benign

0.32

M_CAP

Benign

0.023

MetaRNN

Benign

0.088

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

PhyloP100

-3.1

PrimateAI

Uncertain

0.75

PROVEAN

Benign

-0.62

REVEL

Benign

0.058

Sift

Benign

0.078

Sift4G

Benign

0.063

Polyphen

0.0020

Vest4

0.12

MutPred

0.32

Gain of helix (P = 0.0199)

MVP

0.17

ClinPred

0.11

GERP RS

-1.3

PromoterAI

-0.025

Neutral

(source)

Varity_R

0.048

gMVP

0.35

Mutation Taster

=96/4

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over