chr11-102716306-C-T

Variant names:

• chr11-102716306-C-T
• rs61754773
• NM_002424.3:c.898G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_002424.3(MMP8):​c.898G>A​(p.Asp300Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000233 in 1,564,942 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00019 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00024 (3 hom.)
• Consequence: MMP8 NM_002424.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.38
• Publications: 5 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: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.009745091).
• BP6: Variant 11-102716306-C-T is Benign according to our data. Variant chr11-102716306-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 742574.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome4 at 3 gene

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.898G>A	p.Asp300Asn	missense	Exon 6 of 10	NP_002415.1	P22894
	MMP8	NM_001304441.2		c.829G>A	p.Asp277Asn	missense	Exon 7 of 11	NP_001291370.1
	MMP8	NM_001304442.2		c.829G>A	p.Asp277Asn	missense	Exon 7 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.898G>A	p.Asp300Asn	missense	Exon 6 of 10	ENSP00000236826.3	P22894
	MMP8	ENST00000438475.2	TSL:5	c.823G>A	p.Asp275Asn	missense	Exon 6 of 9	ENSP00000401004.2	H7C1M3
	MMP8	ENST00000528662.6	TSL:5	n.*875G>A		non_coding_transcript_exon	Exon 8 of 12	ENSP00000431431.2	E9PL87

Frequencies

GnomAD3 genomes AF: 0.000194 AC: 29 AN: 149504 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000148

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000679

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00218

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000148

Gnomad OTH AF: 0.000485

GnomAD2 exomes AF: 0.000290 AC: 70 AN: 241792 AF XY: 0.000283

Gnomad AFR exome AF: 0.000313

Gnomad AMR exome AF: 0.0000927

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00325

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000682

GnomAD4 exome AF: 0.000237 AC: 336 AN: 1415324 Hom.: 3 Cov.: 27 AF XY: 0.000231 AC XY: 163 AN XY: 704936

African (AFR) AF: 0.0000946 AC: 3 AN: 31718

American (AMR) AF: 0.0000954 AC: 4 AN: 41918

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24910

East Asian (EAS) AF: 0.00795 AC: 301 AN: 37870

South Asian (SAS) AF: 0.0000120 AC: 1 AN: 83512

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51502

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5578

European-Non Finnish (NFE) AF: 0.0000120 AC: 13 AN: 1080226

Other (OTH) AF: 0.000241 AC: 14 AN: 58090

GnomAD4 genome AF: 0.000187 AC: 28 AN: 149618 Hom.: 0 Cov.: 31 AF XY: 0.000165 AC XY: 12 AN XY: 72764

African (AFR) AF: 0.000147 AC: 6 AN: 40696

American (AMR) AF: 0.000611 AC: 9 AN: 14740

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3456

East Asian (EAS) AF: 0.00219 AC: 11 AN: 5034

South Asian (SAS) AF: 0.00 AC: 0 AN: 4728

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9958

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 284

European-Non Finnish (NFE) AF: 0.0000148 AC: 1 AN: 67728

Other (OTH) AF: 0.000480 AC: 1 AN: 2084

Alfa AF: 0.000148 Hom.: 0

ExAC AF: 0.000288 AC: 35

Asia WGS AF: 0.00231 AC: 8 AN: 3478

EpiCase AF: 0.0000550

EpiControl AF: 0.0000600

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.56	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.12	T
Eigen	Benign	-0.043
Eigen_PC	Benign	-0.051
FATHMM_MKL	Benign	0.72	D
LIST_S2	Benign	0.85	D
M_CAP	Benign	0.0079	T
MetaRNN	Benign	0.0097	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	1.7	L
PhyloP100		2.4
PrimateAI	Benign	0.47	T
PROVEAN	Uncertain	-3.3	D
REVEL	Benign	0.050
Sift	Benign	0.12	T
Sift4G	Benign	0.18	T
Polyphen		0.0070	B
Vest4		0.30
MVP		0.53
MPC		0.049
ClinPred		0.040	T
GERP RS		3.0
Varity_R		0.099
gMVP		0.47
Mutation Taster		=94/6	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: rs61754773; hg19: chr11-102587037;