11-102608807-A-G

Variant names:

• chr11-102608807-A-G
• rs7939224
• NM_004771.4:c.811+130T>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_004771.4(MMP20):​c.811+130T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.232 in 990,358 control chromosomes in the GnomAD database, including 27,776 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.24 (4687 hom., cov: 34)
  • Exomes 𝑓: 0.23 (23089 hom.)
• Consequence: MMP20 NM_004771.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.124
• Publications: 2 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 11-102608807-A-G is Benign according to our data. Variant chr11-102608807-A-G is described in ClinVar as [Benign]. Clinvar id is 1222934.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.278 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MMP20	NM_004771.4	c.811+130T>C		intron_variant	Intron 5 of 9	ENST00000260228.3	NP_004762.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MMP20	ENST00000260228.3	c.811+130T>C		intron_variant	Intron 5 of 9	1	NM_004771.4	ENSP00000260228.2
MMP20-AS1	ENST00000542119.2	n.233+1355A>G		intron_variant	Intron 1 of 3	3
MMP20-AS1	ENST00000782665.1	n.233+1355A>G		intron_variant	Intron 1 of 5

Frequencies

GnomAD3 genomes AF: 0.243 AC: 36940 AN: 152132 Hom.: 4675 Cov.: 34

Gnomad AFR AF: 0.282

Gnomad AMI AF: 0.128

Gnomad AMR AF: 0.249

Gnomad ASJ AF: 0.313

Gnomad EAS AF: 0.0217

Gnomad SAS AF: 0.202

Gnomad FIN AF: 0.216

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.239

Gnomad OTH AF: 0.239

GnomAD4 exome AF: 0.230 AC: 192790 AN: 838108 Hom.: 23089 AF XY: 0.230 AC XY: 101093 AN XY: 440180

African (AFR) AF: 0.283 AC: 5927 AN: 20970

American (AMR) AF: 0.253 AC: 10464 AN: 41346

Ashkenazi Jewish (ASJ) AF: 0.308 AC: 6773 AN: 21970

East Asian (EAS) AF: 0.0325 AC: 1176 AN: 36164

South Asian (SAS) AF: 0.222 AC: 15764 AN: 70996

European-Finnish (FIN) AF: 0.219 AC: 10526 AN: 48068

Middle Eastern (MID) AF: 0.269 AC: 785 AN: 2916

European-Non Finnish (NFE) AF: 0.238 AC: 132124 AN: 555900

Other (OTH) AF: 0.233 AC: 9251 AN: 39778

GnomAD4 genome AF: 0.243 AC: 36980 AN: 152250 Hom.: 4687 Cov.: 34 AF XY: 0.242 AC XY: 17980 AN XY: 74438

African (AFR) AF: 0.282 AC: 11723 AN: 41526

American (AMR) AF: 0.249 AC: 3812 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.313 AC: 1087 AN: 3470

East Asian (EAS) AF: 0.0220 AC: 114 AN: 5192

South Asian (SAS) AF: 0.203 AC: 981 AN: 4826

European-Finnish (FIN) AF: 0.216 AC: 2289 AN: 10602

Middle Eastern (MID) AF: 0.330 AC: 97 AN: 294

European-Non Finnish (NFE) AF: 0.239 AC: 16260 AN: 68020

Other (OTH) AF: 0.237 AC: 500 AN: 2114

Alfa AF: 0.247 Hom.: 585

Bravo AF: 0.243

Asia WGS AF: 0.112 AC: 390 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 19, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	3.2
DANN	Benign	0.77
PhyloP100		0.12
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: rs7939224; hg19: chr11-102479538;