8-88186601-GCAA-G

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_005941.5(MMP16):c.282-6_282-4del variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 0)
  • Exomes 𝑓: 0.00029 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MMP16 NM_005941.5 splice_region, splice_polypyrimidine_tract, intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.62

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 Likely_benign. Variant got -6 ACMG points.

• BP6: Variant 8-88186601-GCAA-G is Benign according to our data. Variant chr8-88186601-GCAA-G is described in ClinVar as [Likely_benign]. Clinvar id is 726095.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAdExome at 19 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MMP16	NM_005941.5	c.282-6_282-4del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000286614.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MMP16	ENST00000286614.11	c.282-6_282-4del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_005941.5	P1
MMP16	ENST00000544227.5	n.282-6_282-4del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant		1
MMP16	ENST00000522726.1	c.333-6_333-4del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		4
MMP16	ENST00000520568.1	n.332-6_332-4del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD3 exomes AF: 0.000217 AC: 19 AN: 87384 Hom.: 0 AF XY: 0.000252 AC XY: 12 AN XY: 47556

Gnomad AFR exome AF: 0.000132

Gnomad AMR exome AF: 0.000557

Gnomad ASJ exome AF: 0.000598

Gnomad EAS exome AF: 0.000148

Gnomad SAS exome AF: 0.000409

Gnomad FIN exome AF: 0.000148

Gnomad NFE exome AF: 0.000150

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000287 AC: 261 AN: 908884 Hom.: 0 AF XY: 0.000357 AC XY: 159 AN XY: 445762

Gnomad4 AFR exome AF: 0.000214

Gnomad4 AMR exome AF: 0.00105

Gnomad4 ASJ exome AF: 0.000244

Gnomad4 EAS exome AF: 0.000401

Gnomad4 SAS exome AF: 0.000779

Gnomad4 FIN exome AF: 0.000218

Gnomad4 NFE exome AF: 0.000239

Gnomad4 OTH exome AF: 0.000411

GnomAD4 genome Cov.: 0

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

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: rs1554584176; hg19: chr8-89198830;