1-1632328-T-C

Variant names:

• chr1-1632328-T-C
• rs1283366598
• NM_006983.2:c.110T>C

Variant summary

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

The NM_006983.2(MMP23B):​c.110T>C​(p.Leu37Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000211 in 1,420,654 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. L37Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 29)
  • Exomes 𝑓: 0.0000016 (0 hom.)
• Consequence: MMP23B NM_006983.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0710
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.110T>C	p.Leu37Pro	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.110T>C	p.Leu37Pro	missense	Exon 1 of 8	ENSP00000348308.5	O75900-1
	MMP23B	ENST00000378675.7	TSL:1	c.110T>C	p.Leu37Pro	missense	Exon 1 of 7	ENSP00000367945.3	O75086
	MMP23B	ENST00000891264.1		c.110T>C	p.Leu37Pro	missense	Exon 1 of 7	ENSP00000561323.1

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 151940 Hom.: 0 Cov.: 29

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000478

GnomAD4 exome AF: 0.00000158 AC: 2 AN: 1268714 Hom.: 0 Cov.: 32 AF XY: 0.00000321 AC XY: 2 AN XY: 622750

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 24766

American (AMR) AF: 0.00 AC: 0 AN: 18722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20486

East Asian (EAS) AF: 0.0000357 AC: 1 AN: 27986

South Asian (SAS) AF: 0.00 AC: 0 AN: 62596

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 30898

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3662

European-Non Finnish (NFE) AF: 9.73e-7 AC: 1 AN: 1027330

Other (OTH) AF: 0.00 AC: 0 AN: 52268

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00666416), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 151940 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 74226

African (AFR) AF: 0.00 AC: 0 AN: 41404

American (AMR) AF: 0.00 AC: 0 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5154

South Asian (SAS) AF: 0.00 AC: 0 AN: 4796

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10598

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67942

Other (OTH) AF: 0.000478 AC: 1 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	-0.074	T
BayesDel_noAF	Benign	-0.34
CADD	Uncertain	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.11	T
Eigen	Benign	-0.0018
Eigen_PC	Benign	-0.14
FATHMM_MKL	Benign	0.39	N
LIST_S2	Benign	0.45	T
M_CAP	Pathogenic	0.68	D
MetaRNN	Uncertain	0.55	D
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	1.0	L
PhyloP100		0.071
PrimateAI	Pathogenic	0.84	D
PROVEAN	Benign	-0.91	N
REVEL	Benign	0.26
Sift	Uncertain	0.012	D
Sift4G	Uncertain	0.020	D
Polyphen		1.0	D
Vest4		0.35
MutPred		0.75		Loss of helix (P = 0.0237)
MVP		0.65
ClinPred		0.50	D
GERP RS		3.2
PromoterAI		-0.0035	Neutral
Varity_R		0.56
gMVP		0.81
Mutation Taster		=70/30	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: rs1283366598; hg19: chr1-1567707;