chr8-88074632-T-C

Variant names:

• chr8-88074632-T-C
• rs61753768
• NM_005941.5:c.1195A>G

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_005941.5(MMP16):​c.1195A>G​(p.Ser399Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00175 in 1,613,408 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00095 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0018 (5 hom.)
• Consequence: MMP16 NM_005941.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.96
• Publications: 5 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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.029503495).
• BS2: High AC in GnomAd4 at 145 AD gene.

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.1195A>G	p.Ser399Gly	missense	Exon 7 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.1195A>G	p.Ser399Gly	missense	Exon 7 of 10	ENSP00000286614.6	P51512-1
	MMP16	ENST00000544227.5	TSL:1	n.1195A>G		non_coding_transcript_exon	Exon 7 of 8

Frequencies

GnomAD3 genomes AF: 0.000953 AC: 145 AN: 152140 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000434

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00181

Gnomad OTH AF: 0.000958

GnomAD2 exomes AF: 0.000810 AC: 203 AN: 250592 AF XY: 0.000827

Gnomad AFR exome AF: 0.000308

Gnomad AMR exome AF: 0.0000871

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000185

Gnomad NFE exome AF: 0.00169

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00184 AC: 2684 AN: 1461268 Hom.: 5 Cov.: 31 AF XY: 0.00188 AC XY: 1365 AN XY: 726942

African (AFR) AF: 0.000209 AC: 7 AN: 33446

American (AMR) AF: 0.0000224 AC: 1 AN: 44652

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26114

East Asian (EAS) AF: 0.00 AC: 0 AN: 39630

South Asian (SAS) AF: 0.00 AC: 0 AN: 86228

European-Finnish (FIN) AF: 0.000393 AC: 21 AN: 53394

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 0.00235 AC: 2609 AN: 1111672

Other (OTH) AF: 0.000745 AC: 45 AN: 60372

GnomAD4 genome AF: 0.000953 AC: 145 AN: 152140 Hom.: 0 Cov.: 32 AF XY: 0.000861 AC XY: 64 AN XY: 74308

African (AFR) AF: 0.000434 AC: 18 AN: 41444

American (AMR) AF: 0.00 AC: 0 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.000188 AC: 2 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00181 AC: 123 AN: 68020

Other (OTH) AF: 0.000958 AC: 2 AN: 2088

Alfa AF: 0.00151 Hom.: 1

Bravo AF: 0.000979

TwinsUK AF: 0.00270 AC: 10

ALSPAC AF: 0.00182 AC: 7

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.00174 AC: 15

ExAC AF: 0.000824 AC: 100

EpiCase AF: 0.00158

EpiControl AF: 0.00184

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.094
BayesDel_addAF	Benign	-0.49	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.12	T
Eigen	Benign	-0.053
Eigen_PC	Benign	0.10
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.0095	T
MetaRNN	Benign	0.030	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	1.2	L
PhyloP100		5.0
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.086
Sift	Benign	0.39	T
Sift4G	Benign	0.41	T
Polyphen		0.0010	B
Vest4		0.48
MVP		0.42
MPC		0.79
ClinPred		0.032	T
GERP RS		4.6
Varity_R		0.21
gMVP		0.57
Mutation Taster		=79/21	polymorphism

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: rs61753768; hg19: chr8-89086860; COSMIC: COSV99075560;