11-102718423-C-A

Variant names:

• chr11-102718423-C-A
• NM_002424.3:c.775G>T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002424.3(MMP8):​c.775G>T​(p.Ala259Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MMP8 NM_002424.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.782

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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05496025).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MMP8	NM_002424.3	c.775G>T	p.Ala259Ser	missense_variant	Exon 5 of 10	ENST00000236826.8	NP_002415.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MMP8	ENST00000236826.8	c.775G>T	p.Ala259Ser	missense_variant	Exon 5 of 10	1	NM_002424.3	ENSP00000236826.3
MMP8	ENST00000438475.2	c.700G>T	p.Ala234Ser	missense_variant	Exon 5 of 9	5		ENSP00000401004.2
MMP8	ENST00000528662.6	n.*752G>T		non_coding_transcript_exon_variant	Exon 7 of 12	5		ENSP00000431431.2
MMP8	ENST00000528662.6	n.*752G>T		3_prime_UTR_variant	Exon 7 of 12	5		ENSP00000431431.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 14, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.775G>T (p.A259S) alteration is located in exon 5 (coding exon 5) of the MMP8 gene. This alteration results from a G to T substitution at nucleotide position 775, causing the alanine (A) at amino acid position 259 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	11
DANN	Benign	0.22
DEOGEN2	Benign	0.029	T
Eigen	Benign	-0.59
Eigen_PC	Benign	-0.61
FATHMM_MKL	Benign	0.23	N
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.0061	T
MetaRNN	Benign	0.055	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.94	L
PrimateAI	Benign	0.27	T
PROVEAN	Benign	0.14	N
REVEL	Benign	0.056
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0030	B
Vest4		0.10
MutPred		0.48		Gain of disorder (P = 0.0188);
MVP		0.27
MPC		0.038
ClinPred		0.050	T
GERP RS		-0.73
Varity_R		0.28
gMVP		0.13

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: chr11-102589154;