8-88039069-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_005941.5(MMP16):c.*2392G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.569 in 152,236 control chromosomes in the GnomAD database, including 24,803 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.57 (24743 hom., cov: 32)
  • Exomes 𝑓: 0.53 (60 hom.)
• Consequence: MMP16 NM_005941.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.26

Genes affected

MMP16 (HGNC:7162): (matrix metallopeptidase 16) 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 encoded protein activates MMP2 by cleavage. This gene was once referred to as MT-MMP2, but was renamed as MT-MMP3 or MMP16. [provided by RefSeq, Oct 2010]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BP6: Variant 8-88039069-C-T is Benign according to our data. Variant chr8-88039069-C-T is described in ClinVar as [Benign]. Clinvar id is 1270817.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.664 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MMP16	NM_005941.5	c.*2392G>A		3_prime_UTR_variant	10/10	ENST00000286614.11
MMP16	XM_024447154.2	c.*2392G>A		3_prime_UTR_variant	7/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MMP16	ENST00000286614.11	c.*2392G>A		3_prime_UTR_variant	10/10	1	NM_005941.5	P1

Frequencies

GnomAD3 genomes AF: 0.569 AC: 86315 AN: 151686 Hom.: 24712 Cov.: 32

Gnomad AFR AF: 0.535

Gnomad AMI AF: 0.672

Gnomad AMR AF: 0.657

Gnomad ASJ AF: 0.584

Gnomad EAS AF: 0.683

Gnomad SAS AF: 0.550

Gnomad FIN AF: 0.514

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.569

Gnomad OTH AF: 0.569

GnomAD4 exome AF: 0.533 AC: 229 AN: 430 Hom.: 60 Cov.: 0 AF XY: 0.504 AC XY: 131 AN XY: 260

Gnomad4 FIN exome AF: 0.531

Gnomad4 NFE exome AF: 0.500

Gnomad4 OTH exome AF: 0.750

GnomAD4 genome AF: 0.569 AC: 86396 AN: 151806 Hom.: 24743 Cov.: 32 AF XY: 0.568 AC XY: 42160 AN XY: 74186

Gnomad4 AFR AF: 0.536

Gnomad4 AMR AF: 0.657

Gnomad4 ASJ AF: 0.584

Gnomad4 EAS AF: 0.683

Gnomad4 SAS AF: 0.547

Gnomad4 FIN AF: 0.514

Gnomad4 NFE AF: 0.569

Gnomad4 OTH AF: 0.570

Alfa AF: 0.573 Hom.: 35508

Bravo AF: 0.578

Asia WGS AF: 0.629 AC: 2180 AN: 3470

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 29, 2020

This variant is associated with the following publications: (PMID: 32196811) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
Cadd	Benign	11
Dann	Benign	0.74

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

Publications

LitVar

Other links and lift over

dbSNP: rs2664370; hg19: chr8-89051297; COSMIC: COSV54187220;