11-102714705-G-A

Variant names:

• chr11-102714705-G-A
• NM_002424.3:c.1041C>T

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_002424.3(MMP8):​c.1041C>T​(p.Asn347Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000015 in 1,336,360 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 0.0000015 (0 hom.)
• Consequence: MMP8 NM_002424.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.79

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 Likely_benign. Variant got -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 11-102714705-G-A is Benign according to our data. Variant chr11-102714705-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2642320.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.79 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MMP8	NM_002424.3	c.1041C>T	p.Asn347Asn	synonymous_variant	Exon 8 of 10	ENST00000236826.8	NP_002415.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MMP8	ENST00000236826.8	c.1041C>T	p.Asn347Asn	synonymous_variant	Exon 8 of 10	1	NM_002424.3	ENSP00000236826.3
MMP8	ENST00000438475.2	c.961+599C>T		intron_variant	Intron 7 of 8	5		ENSP00000401004.2
MMP8	ENST00000528662.6	n.*1018C>T		non_coding_transcript_exon_variant	Exon 10 of 12	5		ENSP00000431431.2
MMP8	ENST00000528662.6	n.*1018C>T		3_prime_UTR_variant	Exon 10 of 12	5		ENSP00000431431.2

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 0.00000150 AC: 2 AN: 1336360 Hom.: 0 Cov.: 30 AF XY: 0.00000151 AC XY: 1 AN XY: 661436

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000154

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.51e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 30

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Apr 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

MMP8: PM2:Supporting, BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	1.5
DANN	Benign	0.57

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-102585436; COSMIC: COSV52634489;