Menu
GeneBe

8-88074696-G-A

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2

The NM_005941.5(MMP16):c.1131C>T(p.Tyr377=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000528 in 1,613,514 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0026 ( 1 hom., cov: 32)
Exomes 𝑓: 0.00031 ( 0 hom. )

Consequence

MMP16
NM_005941.5 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.59
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.44).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 8-88074696-G-A is Benign according to our data. Variant chr8-88074696-G-A is described in ClinVar as [Benign]. Clinvar id is 789604.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=2.59 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 394 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
MMP16NM_005941.5 linkuse as main transcriptc.1131C>T p.Tyr377= synonymous_variant 7/10 ENST00000286614.11
MMP16XM_024447154.2 linkuse as main transcriptc.342C>T p.Tyr114= synonymous_variant 4/7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
MMP16ENST00000286614.11 linkuse as main transcriptc.1131C>T p.Tyr377= synonymous_variant 7/101 NM_005941.5 P1P51512-1
MMP16ENST00000544227.5 linkuse as main transcriptn.1131C>T non_coding_transcript_exon_variant 7/81

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00259
AC:
394
AN:
152066
Hom.:
1
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00906
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000590
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00383
GnomAD3 exomes
AF:
0.000801
AC:
201
AN:
250812
Hom.:
0
AF XY:
0.000538
AC XY:
73
AN XY:
135574
show subpopulations
Gnomad AFR exome
AF:
0.00980
Gnomad AMR exome
AF:
0.000958
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000794
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000310
AC:
453
AN:
1461330
Hom.:
0
Cov.:
31
AF XY:
0.000261
AC XY:
190
AN XY:
726996
show subpopulations
Gnomad4 AFR exome
AF:
0.0103
Gnomad4 AMR exome
AF:
0.000873
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000348
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000180
Gnomad4 OTH exome
AF:
0.000712
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00262
AC:
399
AN:
152184
Hom.:
1
Cov.:
32
AF XY:
0.00225
AC XY:
167
AN XY:
74372
show subpopulations
Gnomad4 AFR
AF:
0.00915
Gnomad4 AMR
AF:
0.000589
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00379
Alfa
AF:
0.00163
Hom.:
1
Bravo
AF:
0.00302
Asia WGS
AF:
0.000289
AC:
1
AN:
3476
EpiCase
AF:
0.0000546
EpiControl
AF:
0.000178

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeAug 16, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.44
Cadd
Benign
7.0
Dann
Benign
0.91

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs28991885; hg19: chr8-89086924; API