rs11225343

Variant names:

• chr11-102608938-G-A
• rs11225343
• NM_004771.4:c.810C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_004771.4(MMP20):​c.810C>T​(p.Tyr270Tyr) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00387 in 1,613,820 control chromosomes in the GnomAD database, including 218 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position has been classified as Pathogenic.

• Frequency:
  • Genomes: 𝑓 0.020 (116 hom., cov: 32)
  • Exomes 𝑓: 0.0022 (102 hom.)
• Consequence: MMP20 NM_004771.4 splice_region, synonymous
• Scores: Splicing: ADA: 0.0004272
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -1.49
• Publications: 7 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 11-102608938-G-A is Benign according to our data. Variant chr11-102608938-G-A is described in ClinVar as Benign. ClinVar VariationId is 301944.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.49 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0685 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.810C>T	p.Tyr270Tyr	splice_region synonymous	Exon 5 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.810C>T	p.Tyr270Tyr	splice_region synonymous	Exon 5 of 10	ENSP00000260228.2	O60882
	MMP20-AS1	ENST00000542119.2	TSL:3	n.233+1486G>A		intron	N/A
	MMP20-AS1	ENST00000782665.1		n.233+1486G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0203 AC: 3089 AN: 152080 Hom.: 117 Cov.: 32

Gnomad AFR AF: 0.0706

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00728

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000294

Gnomad OTH AF: 0.0148

GnomAD2 exomes AF: 0.00538 AC: 1353 AN: 251464 AF XY: 0.00372

Gnomad AFR exome AF: 0.0729

Gnomad AMR exome AF: 0.00379

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000185

Gnomad OTH exome AF: 0.00195

GnomAD4 exome AF: 0.00216 AC: 3155 AN: 1461622 Hom.: 102 Cov.: 32 AF XY: 0.00183 AC XY: 1330 AN XY: 727128

African (AFR) AF: 0.0740 AC: 2476 AN: 33462

American (AMR) AF: 0.00445 AC: 199 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.000116 AC: 10 AN: 86250

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00451 AC: 26 AN: 5760

European-Non Finnish (NFE) AF: 0.000122 AC: 136 AN: 1111794

Other (OTH) AF: 0.00510 AC: 308 AN: 60386

GnomAD4 genome AF: 0.0203 AC: 3095 AN: 152198 Hom.: 116 Cov.: 32 AF XY: 0.0191 AC XY: 1422 AN XY: 74420

African (AFR) AF: 0.0706 AC: 2931 AN: 41508

American (AMR) AF: 0.00720 AC: 110 AN: 15270

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

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000294 AC: 20 AN: 68006

Other (OTH) AF: 0.0147 AC: 31 AN: 2112

Alfa AF: 0.00812 Hom.: 124

Bravo AF: 0.0241

Asia WGS AF: 0.00549 AC: 20 AN: 3478

EpiCase AF: 0.000491

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	Amelogenesis imperfecta hypomaturation type 2A2 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.020
DANN	Benign	0.75
PhyloP100		-1.5
Mutation Taster		=78/22	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00043
dbscSNV1_RF	Benign	0.13
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: rs11225343; hg19: chr11-102479669;