11-102594495-C-T

Position:

• chr11-102594495-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_004771.4(MMP20):​c.1090+126G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.443 in 1,264,810 control chromosomes in the GnomAD database, including 127,194 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.39 (12307 hom., cov: 32)
  • Exomes 𝑓: 0.45 (114887 hom.)
• Consequence: MMP20 NM_004771.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0460

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 11-102594495-C-T is Benign according to our data. Variant chr11-102594495-C-T is described in ClinVar as [Benign]. Clinvar id is 1241687.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.564 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MMP20	NM_004771.4	c.1090+126G>A		intron_variant		ENST00000260228.3	NP_004762.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MMP20	ENST00000260228.3	c.1090+126G>A		intron_variant		1	NM_004771.4	ENSP00000260228	P1

Frequencies

GnomAD3 genomes AF: 0.394 AC: 59885 AN: 151906 Hom.: 12295 Cov.: 32

Gnomad AFR AF: 0.293

Gnomad AMI AF: 0.431

Gnomad AMR AF: 0.420

Gnomad ASJ AF: 0.430

Gnomad EAS AF: 0.386

Gnomad SAS AF: 0.581

Gnomad FIN AF: 0.317

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.446

Gnomad OTH AF: 0.423

GnomAD4 exome AF: 0.450 AC: 500340 AN: 1112786 Hom.: 114887 AF XY: 0.455 AC XY: 255191 AN XY: 560568

Gnomad4 AFR exome AF: 0.284

Gnomad4 AMR exome AF: 0.433

Gnomad4 ASJ exome AF: 0.442

Gnomad4 EAS exome AF: 0.384

Gnomad4 SAS exome AF: 0.570

Gnomad4 FIN exome AF: 0.341

Gnomad4 NFE exome AF: 0.454

Gnomad4 OTH exome AF: 0.441

GnomAD4 genome AF: 0.394 AC: 59913 AN: 152024 Hom.: 12307 Cov.: 32 AF XY: 0.391 AC XY: 29049 AN XY: 74294

Gnomad4 AFR AF: 0.293

Gnomad4 AMR AF: 0.420

Gnomad4 ASJ AF: 0.430

Gnomad4 EAS AF: 0.385

Gnomad4 SAS AF: 0.582

Gnomad4 FIN AF: 0.317

Gnomad4 NFE AF: 0.445

Gnomad4 OTH AF: 0.430

Alfa AF: 0.442 Hom.: 7675

Bravo AF: 0.396

Asia WGS AF: 0.512 AC: 1782 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	9.5
DANN	Benign	0.79

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1711437; hg19: chr11-102465226;