rs17174327

Variant names:

• chr11-102607715-C-T
• rs17174327
• NM_004771.4:c.812-1039G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004771.4(MMP20):​c.812-1039G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0879 in 152,164 control chromosomes in the GnomAD database, including 751 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.088 (751 hom., cov: 32)
  • Exomes 𝑓: 0.094 (0 hom.)
• Consequence: MMP20 NM_004771.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0270
• Publications: 3 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.123 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MMP20	NM_004771.4	MANE Select	c.812-1039G>A		intron	N/A	NP_004762.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MMP20	ENST00000260228.3	TSL:1 MANE Select	c.812-1039G>A		intron	N/A	ENSP00000260228.2
	MMP20-AS1	ENST00000544115.1	TSL:3	n.336C>T		non_coding_transcript_exon	Exon 3 of 3
	MMP20	ENST00000544938.1	TSL:3	n.136G>A		non_coding_transcript_exon	Exon 1 of 5

Frequencies

GnomAD3 genomes AF: 0.0880 AC: 13380 AN: 152014 Hom.: 751 Cov.: 32

Gnomad AFR AF: 0.0215

Gnomad AMI AF: 0.123

Gnomad AMR AF: 0.0725

Gnomad ASJ AF: 0.0994

Gnomad EAS AF: 0.0848

Gnomad SAS AF: 0.0789

Gnomad FIN AF: 0.132

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.125

Gnomad OTH AF: 0.0823

GnomAD4 exome AF: 0.0938 AC: 3 AN: 32 Hom.: 0 Cov.: 0 AF XY: 0.0500 AC XY: 1 AN XY: 20

African (AFR) AF: 0.00 AC: 0 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.115 AC: 3 AN: 26

Other (OTH) AF: 0.00 AC: 0 AN: 2

GnomAD4 genome AF: 0.0879 AC: 13376 AN: 152132 Hom.: 751 Cov.: 32 AF XY: 0.0869 AC XY: 6461 AN XY: 74356

African (AFR) AF: 0.0214 AC: 888 AN: 41518

American (AMR) AF: 0.0725 AC: 1108 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0994 AC: 344 AN: 3462

East Asian (EAS) AF: 0.0848 AC: 438 AN: 5166

South Asian (SAS) AF: 0.0788 AC: 380 AN: 4824

European-Finnish (FIN) AF: 0.132 AC: 1388 AN: 10554

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.126 AC: 8536 AN: 68004

Other (OTH) AF: 0.0814 AC: 172 AN: 2112

Alfa AF: 0.110 Hom.: 132

Bravo AF: 0.0799

Asia WGS AF: 0.0720 AC: 249 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.1
DANN	Benign	0.32
PhyloP100		0.027
Mutation Taster		=100/0	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: rs17174327; hg19: chr11-102478446;