chr1-1632342-G-T

Variant names:

• chr1-1632342-G-T
• rs1203831501
• NM_006983.2:c.124G>T

Variant summary

Our verdict is Likely benign. The variant received -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. 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. 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
• 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: Likely_benign. The variant received -2 ACMG points.

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

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.124G>T	p.Ala42Ser	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.124G>T	p.Ala42Ser	missense	Exon 1 of 8	ENSP00000348308.5	O75900-1
	MMP23B	ENST00000378675.7	TSL:1	c.124G>T	p.Ala42Ser	missense	Exon 1 of 7	ENSP00000367945.3	O75086
	MMP23B	ENST00000891264.1		c.124G>T	p.Ala42Ser	missense	Exon 1 of 7	ENSP00000561323.1

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

African (AFR) AF: 0.00 AC: 0 AN: 24378

American (AMR) AF: 0.00 AC: 0 AN: 16084

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19006

East Asian (EAS) AF: 0.00 AC: 0 AN: 28038

South Asian (SAS) AF: 0.00 AC: 0 AN: 58718

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 30364

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3552

European-Non Finnish (NFE) AF: 9.80e-7 AC: 1 AN: 1020048

Other (OTH) AF: 0.00 AC: 0 AN: 51576

GnomAD4 genome Cov.: 29

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
M_CAP	Uncertain	0.14	D
MetaRNN	Benign	0.064	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N
PhyloP100		-0.72
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	-0.010	N
REVEL	Benign	0.031
Sift	Benign	0.59	T
Sift4G	Benign	0.90	T
Polyphen		0.0	B
Vest4		0.058
MutPred		0.41		Gain of glycosylation at A42 (P = 0.0103)
MVP		0.14
ClinPred		0.028	T
GERP RS		0.11
PromoterAI		-0.029	Neutral
Varity_R		0.080
gMVP		0.34
Mutation Taster		=98/2	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: rs1203831501; hg19: chr1-1567721;