8-88126903-G-T

Variant names:

• chr8-88126903-G-T
• rs10504849
• NM_005941.5:c.710-8042C>A

Variant summary

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

The NM_005941.5(MMP16):​c.710-8042C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.373 in 151,448 control chromosomes in the GnomAD database, including 10,875 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 0.37 (10875 hom., cov: 32)
• Consequence: MMP16 NM_005941.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0420
• Publications: 1 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 (EAS) allele frequency at 95% confidence interval = 0.46 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MMP16	NM_005941.5	c.710-8042C>A		intron_variant	Intron 4 of 9	ENST00000286614.11	NP_005932.2
MMP16	XM_024447154.2	c.-81+1198C>A		intron_variant	Intron 1 of 6		XP_024302922.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MMP16	ENST00000286614.11	c.710-8042C>A		intron_variant	Intron 4 of 9	1	NM_005941.5	ENSP00000286614.6
MMP16	ENST00000544227.5	n.710-8042C>A		intron_variant	Intron 4 of 7	1

Frequencies

GnomAD3 genomes AF: 0.373 AC: 56439 AN: 151330 Hom.: 10861 Cov.: 32

Gnomad AFR AF: 0.454

Gnomad AMI AF: 0.500

Gnomad AMR AF: 0.363

Gnomad ASJ AF: 0.321

Gnomad EAS AF: 0.476

Gnomad SAS AF: 0.355

Gnomad FIN AF: 0.404

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.315

Gnomad OTH AF: 0.378

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

GnomAD4 genome AF: 0.373 AC: 56491 AN: 151448 Hom.: 10875 Cov.: 32 AF XY: 0.377 AC XY: 27842 AN XY: 73946

African (AFR) AF: 0.454 AC: 18771 AN: 41366

American (AMR) AF: 0.363 AC: 5500 AN: 15160

Ashkenazi Jewish (ASJ) AF: 0.321 AC: 1108 AN: 3456

East Asian (EAS) AF: 0.476 AC: 2423 AN: 5088

South Asian (SAS) AF: 0.354 AC: 1703 AN: 4816

European-Finnish (FIN) AF: 0.404 AC: 4246 AN: 10504

Middle Eastern (MID) AF: 0.378 AC: 111 AN: 294

European-Non Finnish (NFE) AF: 0.315 AC: 21366 AN: 67744

Other (OTH) AF: 0.383 AC: 807 AN: 2108

Alfa AF: 0.342 Hom.: 1834

Bravo AF: 0.373

Asia WGS AF: 0.487 AC: 1691 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	1.1
DANN	Benign	0.39
PhyloP100		0.042
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: rs10504849; hg19: chr8-89139132;