1-1632342-G-T

Variant names:

• chr1-1632342-G-T
• NM_006983.2:c.124G>T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_006983.2(MMP23B):​c.124G>T​(p.Ala42Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000799 in 1,251,764 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. 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. A42T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 29)
  • Exomes 𝑓: 8.0e-7 (0 hom.)
• Consequence: MMP23B NM_006983.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.717

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06406438).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MMP23B	NM_006983.2	c.124G>T	p.Ala42Ser	missense_variant	Exon 1 of 8	ENST00000356026.10	NP_008914.1
MMP23B	XM_047432837.1	c.124G>T	p.Ala42Ser	missense_variant	Exon 1 of 8		XP_047288793.1
MMP23B	XM_047432838.1	c.124G>T	p.Ala42Ser	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.124G>T	p.Ala42Ser	missense_variant	Exon 1 of 8	1	NM_006983.2	ENSP00000348308.5
MMP23B	ENST00000378675.7	c.124G>T	p.Ala42Ser	missense_variant	Exon 1 of 7	1		ENSP00000367945.3
MMP23B	ENST00000472264.1	c.124G>T	p.Ala42Ser	missense_variant	Exon 1 of 3	3		ENSP00000424976.1
MMP23B	ENST00000512731.5	n.124G>T		non_coding_transcript_exon_variant	Exon 1 of 6	2		ENSP00000423780.1

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome AF: 7.99e-7 AC: 1 AN: 1251764 Hom.: 0 Cov.: 31 AF XY: 0.00000163 AC XY: 1 AN XY: 612746

Gnomad4 AFR exome AF: 0.00

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: 9.80e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 29

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	11
DANN	Benign	0.65
DEOGEN2	Benign	0.072	T;.;.
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.065	N
LIST_S2	Benign	0.50	T;T;T
M_CAP	Uncertain	0.14	D
MetaRNN	Benign	0.064	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N;.;.
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	-0.010	N;D;N
REVEL	Benign	0.031
Sift	Benign	0.59	T;T;D
Sift4G	Benign	0.90	T;T;T
Polyphen		0.0	B;.;B
Vest4		0.058
MutPred		0.41		Gain of glycosylation at A42 (P = 0.0103);Gain of glycosylation at A42 (P = 0.0103);Gain of glycosylation at A42 (P = 0.0103);
MVP		0.14
ClinPred		0.028	T
GERP RS		0.11
Varity_R		0.080
gMVP		0.34

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-1567721;