chr1-1632324-C-A

Variant names:

• chr1-1632324-C-A
• rs1168869026
• NM_006983.2:c.106C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006983.2(MMP23B):​c.106C>A​(p.Leu36Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000784 in 1,275,984 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L36V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 29)
  • Exomes 𝑓: 7.8e-7 (0 hom.)
• Consequence: MMP23B NM_006983.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.336
• Publications: 0 publications found

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]

ACMG classification

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=0.13777503).

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.106C>A	p.Leu36Met	missense	Exon 1 of 8	NP_008914.1	O75900-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MMP23B	ENST00000356026.10	TSL:1 MANE Select	c.106C>A	p.Leu36Met	missense	Exon 1 of 8	ENSP00000348308.5	O75900-1
	MMP23B	ENST00000378675.7	TSL:1	c.106C>A	p.Leu36Met	missense	Exon 1 of 7	ENSP00000367945.3	O75086
	MMP23B	ENST00000891264.1		c.106C>A	p.Leu36Met	missense	Exon 1 of 7	ENSP00000561323.1

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome AF: 7.84e-7 AC: 1 AN: 1275984 Hom.: 0 Cov.: 32 AF XY: 0.00000160 AC XY: 1 AN XY: 626778

African (AFR) AF: 0.00 AC: 0 AN: 25018

American (AMR) AF: 0.00 AC: 0 AN: 19588

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20982

East Asian (EAS) AF: 0.00 AC: 0 AN: 28218

South Asian (SAS) AF: 0.00 AC: 0 AN: 63824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 31538

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3726

European-Non Finnish (NFE) AF: 9.70e-7 AC: 1 AN: 1030418

Other (OTH) AF: 0.00 AC: 0 AN: 52672

GnomAD4 genome Cov.: 29

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	18
DANN	Benign	0.93
DEOGEN2	Benign	0.083	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.063	N
LIST_S2	Benign	0.33	T
M_CAP	Uncertain	0.21	D
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.0	L
PhyloP100		-0.34
PrimateAI	Pathogenic	0.79	T
PROVEAN	Benign	-0.21	N
REVEL	Benign	0.059
Sift	Uncertain	0.019	D
Sift4G	Uncertain	0.016	D
Polyphen		0.0020	B
Vest4		0.27
MutPred		0.64		Gain of helix (P = 0.062)
MVP		0.10
ClinPred		0.099	T
GERP RS		-3.4
PromoterAI		-0.056	Neutral
Varity_R		0.078
gMVP		0.53
Mutation Taster		=91/9	polymorphism

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

Other links and lift over

dbSNP: rs1168869026; hg19: chr1-1567703;