8-88192609-T-C

Variant names:

• chr8-88192609-T-C
• rs1401862
• NM_005941.5:c.281+4549A>G

Variant summary

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

The NM_005941.5(MMP16):​c.281+4549A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.658 in 152,078 control chromosomes in the GnomAD database, including 35,463 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 0.66 (35463 hom., cov: 32)
• Consequence: MMP16 NM_005941.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.242
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.813 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MMP16	NM_005941.5	c.281+4549A>G		intron_variant	Intron 2 of 9	ENST00000286614.11	NP_005932.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MMP16	ENST00000286614.11	c.281+4549A>G		intron_variant	Intron 2 of 9	1	NM_005941.5	ENSP00000286614.6
MMP16	ENST00000544227.5	n.281+4549A>G		intron_variant	Intron 2 of 7	1
MMP16	ENST00000522726.1	c.332+4549A>G		intron_variant	Intron 3 of 4	4		ENSP00000429147.1
MMP16	ENST00000520568.1	n.331+4549A>G		intron_variant	Intron 2 of 2	2

Frequencies

GnomAD3 genomes AF: 0.658 AC: 100023 AN: 151958 Hom.: 35476 Cov.: 32

Gnomad AFR AF: 0.425

Gnomad AMI AF: 0.817

Gnomad AMR AF: 0.517

Gnomad ASJ AF: 0.690

Gnomad EAS AF: 0.464

Gnomad SAS AF: 0.655

Gnomad FIN AF: 0.819

Gnomad MID AF: 0.624

Gnomad NFE AF: 0.819

Gnomad OTH AF: 0.649

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

GnomAD4 genome AF: 0.658 AC: 100029 AN: 152078 Hom.: 35463 Cov.: 32 AF XY: 0.654 AC XY: 48592 AN XY: 74338

African (AFR) AF: 0.424 AC: 17586 AN: 41460

American (AMR) AF: 0.517 AC: 7885 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.690 AC: 2389 AN: 3464

East Asian (EAS) AF: 0.464 AC: 2400 AN: 5174

South Asian (SAS) AF: 0.655 AC: 3158 AN: 4818

European-Finnish (FIN) AF: 0.819 AC: 8679 AN: 10594

Middle Eastern (MID) AF: 0.626 AC: 184 AN: 294

European-Non Finnish (NFE) AF: 0.818 AC: 55647 AN: 67990

Other (OTH) AF: 0.641 AC: 1356 AN: 2116

Alfa AF: 0.772 Hom.: 22726

Bravo AF: 0.624

Asia WGS AF: 0.520 AC: 1814 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.8
DANN	Benign	0.65
PhyloP100		0.24
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: rs1401862; hg19: chr8-89204838;