11-102715443-G-C

Variant names:

• chr11-102715443-G-C
• rs34799325
• NM_002424.3:c.903-6C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002424.3(MMP8):​c.903-6C>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,456,376 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: MMP8 NM_002424.3 splice_region, intron
• Scores: Splicing: ADA: 0.007810
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.750
• Publications: 2 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).

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.903-6C>G		splice_region intron	N/A	NP_002415.1	P22894
	MMP8	NM_001304441.2		c.834-6C>G		splice_region intron	N/A	NP_001291370.1
	MMP8	NM_001304442.2		c.834-6C>G		splice_region intron	N/A	NP_001291371.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MMP8	ENST00000236826.8	TSL:1 MANE Select	c.903-6C>G		splice_region intron	N/A	ENSP00000236826.3	P22894
	MMP8	ENST00000438475.2	TSL:5	c.828-6C>G		splice_region intron	N/A	ENSP00000401004.2	H7C1M3
	MMP8	ENST00000528662.6	TSL:5	n.*880-6C>G		splice_region intron	N/A	ENSP00000431431.2	E9PL87

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.00000410 AC: 1 AN: 244142 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1456376 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 724448

African (AFR) AF: 0.00 AC: 0 AN: 33124

American (AMR) AF: 0.00 AC: 0 AN: 43830

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25756

East Asian (EAS) AF: 0.00 AC: 0 AN: 39644

South Asian (SAS) AF: 0.0000117 AC: 1 AN: 85404

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53020

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5720

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1109722

Other (OTH) AF: 0.00 AC: 0 AN: 60156

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.26
DANN	Benign	0.37
PhyloP100		-0.75

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0078
dbscSNV1_RF	Benign	0.10
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: rs34799325; hg19: chr11-102586174;