1-1634539-G-A

Variant names:

• chr1-1634539-G-A
• NM_006983.2:c.1087G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_006983.2(MMP23B):​c.1087G>A​(p.Val363Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 0.000013 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MMP23B NM_006983.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.25
• 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 -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.039563894).
• BP6: Variant 1-1634539-G-A is Benign according to our data. Variant chr1-1634539-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2524942.Status of the report is criteria_provided_single_submitter, 1 stars.

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.1087G>A	p.Val363Ile	missense	Exon 8 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.1087G>A	p.Val363Ile	missense	Exon 8 of 8	ENSP00000348308.5	O75900-1
	MMP23B	ENST00000378675.7	TSL:1	c.1154G>A	p.Arg385His	missense	Exon 7 of 7	ENSP00000367945.3	O75086
	MMP23B	ENST00000503792.1	TSL:1	c.770G>A	p.Arg257His	missense	Exon 5 of 5	ENSP00000426857.1	H0YAE5

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000126 AC: 12 AN: 953444 Hom.: 0 Cov.: 13 AF XY: 0.0000104 AC XY: 5 AN XY: 482132

⚠️ 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: 24640

American (AMR) AF: 0.00 AC: 0 AN: 32682

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20194

East Asian (EAS) AF: 0.00 AC: 0 AN: 33192

South Asian (SAS) AF: 0.00 AC: 0 AN: 65666

European-Finnish (FIN) AF: 0.0000229 AC: 1 AN: 43758

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3208

European-Non Finnish (NFE) AF: 0.0000160 AC: 11 AN: 687102

Other (OTH) AF: 0.00 AC: 0 AN: 43002

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0000000174519), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 23

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.055
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	3.7
DANN	Benign	0.85
DEOGEN2	Benign	0.017	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-0.95
FATHMM_MKL	Benign	0.28	N
LIST_S2	Benign	0.37	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.040	T
MetaSVM	Benign	-0.93	T
PhyloP100		1.3
PROVEAN	Benign	-0.12	N
REVEL	Benign	0.090
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.0	B
Vest4		0.11
MutPred		0.16		Loss of MoRF binding (P = 0.0226)
MVP		0.12
ClinPred		0.070	T
GERP RS		1.3
Varity_R		0.021
Mutation Taster		=85/15	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

hg19: chr1-1569915;