rs563971507

Variant names:

• chr22-23779272-C-G
• NM_005940.5:c.194C>G

Your query was ambiguous. Multiple possible variants found:

• chr22-23779272-C-G
• chr22-23779272-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005940.5(MMP11):​c.194C>G​(p.Thr65Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000343 in 1,457,454 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T65M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: MMP11 NM_005940.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.727

Genes affected

MMP11 (HGNC:7157): (matrix metallopeptidase 11) Proteins of the matrix metalloproteinase (MMP) family are involved in the breakdown of extracellular matrix in normal physiological processes, such as embryonic development, reproduction, and tissue remodeling, as well as in disease processes, such as arthritis and metastasis. Most MMP's are secreted as inactive proproteins which are activated when cleaved by extracellular proteinases. However, the enzyme encoded by this gene is activated intracellularly by furin within the constitutive secretory pathway. Also in contrast to other MMP's, this enzyme cleaves alpha 1-proteinase inhibitor but weakly degrades structural proteins of the extracellular matrix. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10956851).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MMP11	NM_005940.5	c.194C>G	p.Thr65Arg	missense_variant	Exon 2 of 8	ENST00000215743.8	NP_005931.2
MMP11	NR_133013.2	n.216C>G		non_coding_transcript_exon_variant	Exon 2 of 8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MMP11	ENST00000215743.8	c.194C>G	p.Thr65Arg	missense_variant	Exon 2 of 8	1	NM_005940.5	ENSP00000215743.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000343 AC: 5 AN: 1457454 Hom.: 0 Cov.: 33 AF XY: 0.00000414 AC XY: 3 AN XY: 724746

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000360

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	9.2
DANN	Benign	0.94
DEOGEN2	Benign	0.40	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.047	N
M_CAP	Benign	0.0080	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.5	L
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.030
Sift	Benign	0.31	T
Sift4G	Benign	0.46	T
Polyphen		0.20	B
Vest4		0.28
MutPred		0.25		Loss of phosphorylation at T65 (P = 0.0047);
MVP		0.35
MPC		0.36
ClinPred		0.094	T
GERP RS		-1.7
Varity_R		0.056
gMVP		0.75

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: chr22-24121459;