dbSNP rs2664370: MMP16:c.*2392G>A (chr8-88039069-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_005941.5(MMP16):c.*2392G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.569 in 152,236 control chromosomes in the GnomAD database, including 24,803 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.57 ( 24743 hom., cov: 32)

Exomes 𝑓: 0.53 ( 60 hom. )

Consequence

MMP16
NM_005941.5 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.26

Publications

11 publications found

Variant links:

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]

MMP16 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.58).

BP6

Variant 8-88039069-C-T is Benign according to our data. Variant chr8-88039069-C-T is described in ClinVar as Benign. ClinVar VariationId is 1270817.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.664 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005941.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MMP16	NM_005941.5	MANE Select	c.*2392G>A		3_prime_UTR	Exon 10 of 10	NP_005932.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MMP16	ENST00000286614.11	TSL:1 MANE Select	c.*2392G>A		3_prime_UTR	Exon 10 of 10	ENSP00000286614.6	P51512-1

Frequencies

GnomAD3 genomes

AF:

0.569

AC:

86315

AN:

151686

Hom.:

24712

Cov.:

show subpopulations

Gnomad AFR

AF:

0.535

Gnomad AMI

AF:

0.672

Gnomad AMR

AF:

0.657

Gnomad ASJ

AF:

0.584

Gnomad EAS

AF:

0.683

Gnomad SAS

AF:

0.550

Gnomad FIN

AF:

0.514

Gnomad MID

AF:

0.516

Gnomad NFE

AF:

0.569

Gnomad OTH

AF:

0.569

GnomAD4 exome

AF:

0.533

AC:

229

AN:

430

Hom.:

Cov.:

AF XY:

0.504

AC XY:

131

AN XY:

260

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.531

AC:

225

AN:

424

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.500

AC:

AN:

Other (OTH)

AF:

0.750

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.569

AC:

86396

AN:

151806

Hom.:

24743

Cov.:

AF XY:

0.568

AC XY:

42160

AN XY:

74186

show subpopulations

African (AFR)

AF:

0.536

AC:

22166

AN:

41384

American (AMR)

AF:

0.657

AC:

10013

AN:

15230

Ashkenazi Jewish (ASJ)

AF:

0.584

AC:

2023

AN:

3466

East Asian (EAS)

AF:

0.683

AC:

3510

AN:

5138

South Asian (SAS)

AF:

0.547

AC:

2644

AN:

4830

European-Finnish (FIN)

AF:

0.514

AC:

5424

AN:

10548

Middle Eastern (MID)

AF:

0.537

AC:

158

AN:

294

European-Non Finnish (NFE)

AF:

0.569

AC:

38646

AN:

67900

Other (OTH)

AF:

0.570

AC:

1203

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1893

3786

5678

7571

9464

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

732

1464

2196

2928

3660

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.572

Hom.:

44377

Bravo

AF:

0.578

Asia WGS

AF:

0.629

AC:

2180

AN:

3470

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.58

CADD

Benign

(source)

DANN

Benign

0.74

PhyloP100

1.3

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over