chr11-102625267-T-G

Variant names:

• chr11-102625267-T-G
• rs2245803
• NM_004771.4:c.53A>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_004771.4(MMP20):​c.53A>C​(p.Lys18Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.655 in 1,613,374 control chromosomes in the GnomAD database, including 347,848 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.65 (32181 hom., cov: 30)
  • Exomes 𝑓: 0.66 (315667 hom.)
• Consequence: MMP20 NM_004771.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 1.99
• Publications: 48 publications found

Genes affected

MMP20 (HGNC:7167): (matrix metallopeptidase 20) 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. Most MMP's are secreted as inactive proproteins which are activated when cleaved by extracellular proteinases. The protein encoded by this gene degrades amelogenin, the major protein component of dental enamel matrix, and thus thought to play a role in tooth enamel formation. A mutation in this gene, which alters the normal splice pattern and results in premature termination of the encoded protein, has been associated with amelogenesis imperfecta. This gene is part of a cluster of MMP genes located on chromosome 11q22.3. [provided by RefSeq, Aug 2011]

MMP20-AS1 (HGNC:56362): (MMP20 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.2664314E-6).
• BP6: Variant 11-102625267-T-G is Benign according to our data. Variant chr11-102625267-T-G is described in ClinVar as Benign. ClinVar VariationId is 259539.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.809 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004771.4. 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
	MMP20	NM_004771.4	MANE Select	c.53A>C	p.Lys18Thr	missense	Exon 1 of 10	NP_004762.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MMP20	ENST00000260228.3	TSL:1 MANE Select	c.53A>C	p.Lys18Thr	missense	Exon 1 of 10	ENSP00000260228.2	O60882
	MMP20-AS1	ENST00000542119.2	TSL:3	n.234-1392T>G		intron	N/A
	MMP20-AS1	ENST00000782665.1		n.590-1392T>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.649 AC: 98565 AN: 151816 Hom.: 32142 Cov.: 30

Gnomad AFR AF: 0.625

Gnomad AMI AF: 0.754

Gnomad AMR AF: 0.673

Gnomad ASJ AF: 0.594

Gnomad EAS AF: 0.830

Gnomad SAS AF: 0.711

Gnomad FIN AF: 0.653

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.642

Gnomad OTH AF: 0.658

GnomAD2 exomes AF: 0.665 AC: 167017 AN: 251102 AF XY: 0.667

Gnomad AFR exome AF: 0.623

Gnomad AMR exome AF: 0.670

Gnomad ASJ exome AF: 0.606

Gnomad EAS exome AF: 0.833

Gnomad FIN exome AF: 0.647

Gnomad NFE exome AF: 0.643

Gnomad OTH exome AF: 0.650

GnomAD4 exome AF: 0.656 AC: 958554 AN: 1461438 Hom.: 315667 Cov.: 48 AF XY: 0.656 AC XY: 477161 AN XY: 727022

African (AFR) AF: 0.621 AC: 20785 AN: 33474

American (AMR) AF: 0.674 AC: 30150 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.608 AC: 15873 AN: 26126

East Asian (EAS) AF: 0.842 AC: 33409 AN: 39686

South Asian (SAS) AF: 0.695 AC: 59899 AN: 86244

European-Finnish (FIN) AF: 0.642 AC: 34288 AN: 53378

Middle Eastern (MID) AF: 0.688 AC: 3926 AN: 5706

European-Non Finnish (NFE) AF: 0.648 AC: 720308 AN: 1111738

Other (OTH) AF: 0.661 AC: 39916 AN: 60376

GnomAD4 genome AF: 0.649 AC: 98662 AN: 151936 Hom.: 32181 Cov.: 30 AF XY: 0.653 AC XY: 48460 AN XY: 74250

African (AFR) AF: 0.625 AC: 25899 AN: 41436

American (AMR) AF: 0.673 AC: 10272 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.594 AC: 2059 AN: 3466

East Asian (EAS) AF: 0.829 AC: 4286 AN: 5168

South Asian (SAS) AF: 0.711 AC: 3420 AN: 4812

European-Finnish (FIN) AF: 0.653 AC: 6871 AN: 10524

Middle Eastern (MID) AF: 0.609 AC: 179 AN: 294

European-Non Finnish (NFE) AF: 0.642 AC: 43590 AN: 67948

Other (OTH) AF: 0.663 AC: 1400 AN: 2112

Alfa AF: 0.649 Hom.: 101567

Bravo AF: 0.653

TwinsUK AF: 0.653 AC: 2423

ALSPAC AF: 0.645 AC: 2485

ESP6500AA AF: 0.624 AC: 2751

ESP6500EA AF: 0.644 AC: 5538

ExAC AF: 0.662 AC: 80346

Asia WGS AF: 0.795 AC: 2764 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Amelogenesis imperfecta hypomaturation type 2A2 (2)
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.098
BayesDel_addAF	Benign	-0.69	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	17
DANN	Benign	0.86
DEOGEN2	Benign	0.035	T
Eigen	Benign	-0.57
Eigen_PC	Benign	-0.39
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Benign	0.58	T
MetaRNN	Benign	0.0000013	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		2.0
PrimateAI	Benign	0.43	T
PROVEAN	Benign	0.46	N
REVEL	Benign	0.075
Sift	Benign	0.43	T
Sift4G	Benign	0.55	T
Polyphen		0.0	B
Vest4		0.16
MPC		0.039
ClinPred		0.012	T
GERP RS		4.1
PromoterAI		0.070	Neutral
Varity_R		0.060
gMVP		0.47
Mutation Taster		=93/7	polymorphism (auto)

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: rs2245803; hg19: chr11-102495998; COSMIC: COSV52776019;