rs10504847

chr8-88205981-G-Achr8-88205981-G-Cchr8-88205981-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005941.5(MMP16):c.133-8675C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0692 in 151,534 control chromosomes in the GnomAD database, including 401 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 0.069 (401 hom., cov: 32)
• Consequence: MMP16 NM_005941.5 intron
• Clinical Significance: Not reported in ClinVar
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0963 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MMP16	NM_005941.5	c.133-8675C>T		intron_variant		ENST00000286614.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MMP16	ENST00000286614.11	c.133-8675C>T		intron_variant		1	NM_005941.5	P1
MMP16	ENST00000544227.5	n.133-8675C>T		intron_variant, non_coding_transcript_variant		1
MMP16	ENST00000522726.1	c.184-8675C>T		intron_variant		4
MMP16	ENST00000520568.1	n.183-8675C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0691 AC: 10468 AN: 151416 Hom.: 398 Cov.: 32

Gnomad AFR AF: 0.0987

Gnomad AMI AF: 0.0253

Gnomad AMR AF: 0.0632

Gnomad ASJ AF: 0.0620

Gnomad EAS AF: 0.00717

Gnomad SAS AF: 0.0720

Gnomad FIN AF: 0.0589

Gnomad MID AF: 0.0732

Gnomad NFE AF: 0.0594

Gnomad OTH AF: 0.0735

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0692 AC: 10484 AN: 151534 Hom.: 401 Cov.: 32 AF XY: 0.0685 AC XY: 5071 AN XY: 74020

Gnomad4 AFR AF: 0.0988

Gnomad4 AMR AF: 0.0630

Gnomad4 ASJ AF: 0.0620

Gnomad4 EAS AF: 0.00699

Gnomad4 SAS AF: 0.0720

Gnomad4 FIN AF: 0.0589

Gnomad4 NFE AF: 0.0594

Gnomad4 OTH AF: 0.0741

Alfa AF: 0.0599 Hom.: 306

Bravo AF: 0.0697

Asia WGS AF: 0.0520 AC: 180 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	0.64
Dann	Benign	0.75

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: rs10504847; hg19: chr8-89218210;