1-1634513-C-T

Variant names:

• chr1-1634513-C-T
• rs764972306
• NM_006983.2:c.1061C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_006983.2(MMP23B):​c.1061C>T​(p.Ala354Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000014 (0 hom., cov: 23)
  • Exomes 𝑓: 0.0000041 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MMP23B NM_006983.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.03
• 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.

• BP4: Computational evidence support a benign effect (MetaRNN=0.012294024).

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.1061C>T	p.Ala354Val	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.1061C>T	p.Ala354Val	missense	Exon 8 of 8	ENSP00000348308.5	O75900-1
	MMP23B	ENST00000378675.7	TSL:1	c.1128C>T	p.Gly376Gly	synonymous	Exon 7 of 7	ENSP00000367945.3	O75086
	MMP23B	ENST00000503792.1	TSL:1	c.744C>T	p.Gly248Gly	synonymous	Exon 5 of 5	ENSP00000426857.1	H0YAE5

Frequencies

GnomAD3 genomes AF: 0.0000136 AC: 2 AN: 147118 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000674

Gnomad ASJ AF: 0.000295

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: 0.00

GnomAD2 exomes AF: 0.0000652 AC: 9 AN: 137996 AF XY: 0.0000265

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000567

Gnomad NFE exome AF: 0.0000530

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000407 AC: 4 AN: 981846 Hom.: 0 Cov.: 14 AF XY: 0.00000202 AC XY: 1 AN XY: 494416

African (AFR) AF: 0.00 AC: 0 AN: 25074

American (AMR) AF: 0.0000310 AC: 1 AN: 32234

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20090

East Asian (EAS) AF: 0.00 AC: 0 AN: 33186

South Asian (SAS) AF: 0.00 AC: 0 AN: 65366

European-Finnish (FIN) AF: 0.0000224 AC: 1 AN: 44644

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3248

European-Non Finnish (NFE) AF: 0.00000140 AC: 1 AN: 714068

Other (OTH) AF: 0.0000228 AC: 1 AN: 43936

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000136 AC: 2 AN: 147230 Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0 AN XY: 71614

African (AFR) AF: 0.00 AC: 0 AN: 40522

American (AMR) AF: 0.0000673 AC: 1 AN: 14854

Ashkenazi Jewish (ASJ) AF: 0.000295 AC: 1 AN: 3390

East Asian (EAS) AF: 0.00 AC: 0 AN: 4660

South Asian (SAS) AF: 0.00 AC: 0 AN: 4410

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10272

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 286

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 65980

Other (OTH) AF: 0.00 AC: 0 AN: 1994

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.0000910 AC: 9

ClinVar

ClinVar submissions

Significance: Uncertain significance

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	0.15
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.59
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.10	T
Eigen	Benign	-0.20
Eigen_PC	Benign	-0.24
FATHMM_MKL	Benign	0.62	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.044	D
MetaRNN	Benign	0.012	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.1	L
PhyloP100		2.0
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.081
Sift	Benign	0.091	T
Sift4G	Benign	0.29	T
Polyphen		0.99	D
Vest4		0.25
MVP		0.21
ClinPred		0.27	T
GERP RS		2.6
Varity_R		0.071
gMVP		0.51
Mutation Taster		=93/7	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: rs764972306; hg19: chr1-1569889;