rs3851539

Positions:

• chr8-88310676-G-A
• chr8-88310676-G-C

Variant summary

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

The NM_005941.5(MMP16):​c.132+16399C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.465 in 152,036 control chromosomes in the GnomAD database, including 17,810 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 0.46 (17810 hom., cov: 33)
• Consequence: MMP16 NM_005941.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.74

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=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.577 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MMP16	NM_005941.5	c.132+16399C>T		intron_variant		ENST00000286614.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MMP16	ENST00000286614.11	c.132+16399C>T		intron_variant		1	NM_005941.5	P1
MMP16	ENST00000544227.5	n.132+16399C>T		intron_variant, non_coding_transcript_variant		1
MMP16	ENST00000522726.1	c.183+16399C>T		intron_variant		4
MMP16	ENST00000520568.1	n.182+16399C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.465 AC: 70651 AN: 151918 Hom.: 17811 Cov.: 33

Gnomad AFR AF: 0.281

Gnomad AMI AF: 0.478

Gnomad AMR AF: 0.374

Gnomad ASJ AF: 0.478

Gnomad EAS AF: 0.444

Gnomad SAS AF: 0.440

Gnomad FIN AF: 0.588

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.582

Gnomad OTH AF: 0.444

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

GnomAD4 genome AF: 0.465 AC: 70644 AN: 152036 Hom.: 17810 Cov.: 33 AF XY: 0.462 AC XY: 34308 AN XY: 74324

Gnomad4 AFR AF: 0.281

Gnomad4 AMR AF: 0.374

Gnomad4 ASJ AF: 0.478

Gnomad4 EAS AF: 0.445

Gnomad4 SAS AF: 0.443

Gnomad4 FIN AF: 0.588

Gnomad4 NFE AF: 0.582

Gnomad4 OTH AF: 0.439

Alfa AF: 0.550 Hom.: 47965

Bravo AF: 0.442

Asia WGS AF: 0.378 AC: 1319 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	4.8
DANN	Benign	0.65

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: rs3851539; hg19: chr8-89322905;