chr11-102714584-A-G

Variant names:

• chr11-102714584-A-G
• rs776492098
• NM_002424.3:c.1162T>C

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_002424.3(MMP8):​c.1162T>C​(p.Tyr388His) variant causes a missense change. The variant allele was found at a frequency of 0.00000445 in 1,348,158 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000045 (0 hom.)
• Consequence: MMP8 NM_002424.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.83
• Publications: 0 publications found

Genes affected

MMP8 (HGNC:7175): (matrix metallopeptidase 8) This gene encodes a member of the matrix metalloproteinase (MMP) family of proteins. These proteins are involved in the breakdown of extracellular matrix in embryonic development, reproduction, and tissue remodeling, as well as in disease processes, such as arthritis and metastasis. Proteolysis at different sites on this protein results in multiple active forms of the enzyme with distinct N-termini. This protein functions in the degradation of type I, II and III collagens. The gene is part of a cluster of MMP genes which localize to chromosome 11q22.3. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2015]

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.763

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002424.3. 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
	MMP8	NM_002424.3	MANE Select	c.1162T>C	p.Tyr388His	missense	Exon 8 of 10	NP_002415.1	P22894
	MMP8	NM_001304441.2		c.1093T>C	p.Tyr365His	missense	Exon 9 of 11	NP_001291370.1
	MMP8	NM_001304442.2		c.1093T>C	p.Tyr365His	missense	Exon 9 of 11	NP_001291371.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MMP8	ENST00000236826.8	TSL:1 MANE Select	c.1162T>C	p.Tyr388His	missense	Exon 8 of 10	ENSP00000236826.3	P22894
	MMP8	ENST00000438475.2	TSL:5	c.961+720T>C		intron	N/A	ENSP00000401004.2	H7C1M3
	MMP8	ENST00000528662.6	TSL:5	n.*1139T>C		non_coding_transcript_exon	Exon 10 of 12	ENSP00000431431.2	E9PL87

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.0000166 AC: 3 AN: 180214 AF XY: 0.0000201

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000968

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000111

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000445 AC: 6 AN: 1348158 Hom.: 0 Cov.: 30 AF XY: 0.00000299 AC XY: 2 AN XY: 668876

African (AFR) AF: 0.00 AC: 0 AN: 27764

American (AMR) AF: 0.00 AC: 0 AN: 26400

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22624

East Asian (EAS) AF: 0.0000303 AC: 1 AN: 33012

South Asian (SAS) AF: 0.0000147 AC: 1 AN: 68026

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51402

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5424

European-Non Finnish (NFE) AF: 0.00000378 AC: 4 AN: 1058374

Other (OTH) AF: 0.00 AC: 0 AN: 55132

GnomAD4 genome Cov.: 31

ExAC AF: 0.0000165 AC: 2

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	Uncertain	0.44
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.18
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.29	T
Eigen	Pathogenic	0.72
Eigen_PC	Uncertain	0.64
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.013	T
MetaRNN	Pathogenic	0.76	D
MetaSVM	Benign	-0.82	T
MutationAssessor	Pathogenic	3.5	M
PhyloP100		3.8
PrimateAI	Uncertain	0.53	T
PROVEAN	Uncertain	-4.0	D
REVEL	Benign	0.26
Sift	Uncertain	0.0070	D
Sift4G	Pathogenic	0.0010	D
Polyphen		0.99	D
Vest4		0.56
MutPred		0.78		Loss of stability (P = 0.0776)
MVP		0.59
MPC		0.31
ClinPred		0.95	D
GERP RS		5.5
Varity_R		0.39
gMVP		0.64
Mutation Taster		=80/20	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs776492098; hg19: chr11-102585315;