11-102713365-T-C

Position:

• chr11-102713365-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The ENST00000236826.8(MMP8):​c.1387A>G​(p.Asn463Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00121 in 1,612,686 control chromosomes in the GnomAD database, including 21 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0065 (13 hom., cov: 33)
  • Exomes 𝑓: 0.00066 (8 hom.)
• Consequence: MMP8 ENST00000236826.8 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.34

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

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.011686385).
• BP6: Variant 11-102713365-T-C is Benign according to our data. Variant chr11-102713365-T-C is described in ClinVar as [Benign]. Clinvar id is 714053.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00647 (985/152336) while in subpopulation AFR AF= 0.0226 (941/41586). AF 95% confidence interval is 0.0214. There are 13 homozygotes in gnomad4. There are 459 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 13 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MMP8	NM_002424.3	c.1387A>G	p.Asn463Asp	missense_variant	10/10	ENST00000236826.8	NP_002415.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MMP8	ENST00000236826.8	c.1387A>G	p.Asn463Asp	missense_variant	10/10	1	NM_002424.3	ENSP00000236826	P1
MMP8	ENST00000438475.2	c.*126A>G		3_prime_UTR_variant	9/9	5		ENSP00000401004
MMP8	ENST00000528662.6	c.*1364A>G		3_prime_UTR_variant, NMD_transcript_variant	12/12	5		ENSP00000431431

Frequencies

GnomAD3 genomes AF: 0.00646 AC: 983 AN: 152218 Hom.: 13 Cov.: 33

Gnomad AFR AF: 0.0226

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00190

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: 0.000132

Gnomad OTH AF: 0.00287

GnomAD3 exomes AF: 0.00174 AC: 435 AN: 250688 Hom.: 5 AF XY: 0.00117 AC XY: 159 AN XY: 135466

Gnomad AFR exome AF: 0.0235

Gnomad AMR exome AF: 0.00125

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: 0.0000707

Gnomad OTH exome AF: 0.000327

GnomAD4 exome AF: 0.000659 AC: 962 AN: 1460350 Hom.: 8 Cov.: 30 AF XY: 0.000570 AC XY: 414 AN XY: 726560

Gnomad4 AFR exome AF: 0.0229

Gnomad4 AMR exome AF: 0.00157

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000189

Gnomad4 OTH exome AF: 0.00164

GnomAD4 genome AF: 0.00647 AC: 985 AN: 152336 Hom.: 13 Cov.: 33 AF XY: 0.00616 AC XY: 459 AN XY: 74480

Gnomad4 AFR AF: 0.0226

Gnomad4 AMR AF: 0.00190

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000132

Gnomad4 OTH AF: 0.00284

Alfa AF: 0.00142 Hom.: 5

Bravo AF: 0.00739

ESP6500AA AF: 0.0209 AC: 92

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.00213 AC: 258

Asia WGS AF: 0.00260 AC: 10 AN: 3478

EpiCase AF: 0.0000546

EpiControl AF: 0.00

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 15, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.63	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Benign	0.25	T
Eigen	Benign	-0.33
Eigen_PC	Benign	-0.23
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.37	T
MetaRNN	Benign	0.012	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.4	M
MutationTaster	Benign	0.92	D
PrimateAI	Uncertain	0.54	T
PROVEAN	Uncertain	-2.8	D
REVEL	Benign	0.074
Sift	Benign	0.11	T
Sift4G	Benign	0.33	T
Polyphen		0.014	B
Vest4		0.39
MVP		0.43
MPC		0.29
ClinPred		0.017	T
GERP RS		4.5
Varity_R		0.18
gMVP		0.43

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

Other links and lift over

dbSNP: rs77504671; hg19: chr11-102584096;