1-1632351-G-A

Variant names:

• chr1-1632351-G-A
• rs912489128
• NM_006983.2:c.133G>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006983.2(MMP23B):​c.133G>A​(p.Val45Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000161 in 1,238,984 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0850

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1304304).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MMP23B	NM_006983.2	c.133G>A	p.Val45Met	missense_variant	Exon 1 of 8	ENST00000356026.10	NP_008914.1
MMP23B	XM_047432837.1	c.133G>A	p.Val45Met	missense_variant	Exon 1 of 8		XP_047288793.1
MMP23B	XM_047432838.1	c.133G>A	p.Val45Met	missense_variant	Exon 1 of 8		XP_047288794.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MMP23B	ENST00000356026.10	c.133G>A	p.Val45Met	missense_variant	Exon 1 of 8	1	NM_006983.2	ENSP00000348308.5
MMP23B	ENST00000378675.7	c.133G>A	p.Val45Met	missense_variant	Exon 1 of 7	1		ENSP00000367945.3
MMP23B	ENST00000472264.1	c.133G>A	p.Val45Met	missense_variant	Exon 1 of 3	3		ENSP00000424976.1
MMP23B	ENST00000512731.5	n.133G>A		non_coding_transcript_exon_variant	Exon 1 of 6	2		ENSP00000423780.1

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome AF: 0.00000161 AC: 2 AN: 1238984 Hom.: 0 Cov.: 31 AF XY: 0.00000165 AC XY: 1 AN XY: 605156

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000742

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: 9.85e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 29

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 02, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.133G>A (p.V45M) alteration is located in exon 1 (coding exon 1) of the MMP23B gene. This alteration results from a G to A substitution at nucleotide position 133, causing the valine (V) at amino acid position 45 to be replaced by a methionine (M). 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	-0.19	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	7.5
DANN	Benign	0.94
DEOGEN2	Benign	0.076	T;.;.
Eigen	Benign	-0.88
Eigen_PC	Benign	-0.93
FATHMM_MKL	Benign	0.066	N
LIST_S2	Benign	0.44	T;T;T
M_CAP	Benign	0.0055	T
MetaRNN	Benign	0.13	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N;.;.
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-0.060	N;D;N
REVEL	Benign	0.040
Sift	Benign	0.23	T;D;D
Sift4G	Benign	0.10	T;D;T
Polyphen		0.026	B;.;B
Vest4		0.089
MutPred		0.56		Gain of glycosylation at P43 (P = 0.0871);Gain of glycosylation at P43 (P = 0.0871);Gain of glycosylation at P43 (P = 0.0871);
MVP		0.14
ClinPred		0.11	T
GERP RS		0.84
Varity_R		0.029
gMVP		0.37

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

Other links and lift over

dbSNP: rs912489128; hg19: chr1-1567730;