chr13-52733328-T-C
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_007015.3(CNMD):c.245A>G(p.Asn82Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,628 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000034 ( 0 hom. )
Consequence
CNMD
NM_007015.3 missense
NM_007015.3 missense
Scores
2
7
8
Clinical Significance
Conservation
PhyloP100: 7.45
Genes affected
CNMD (HGNC:17005): (chondromodulin) This gene encodes a glycosylated transmembrane protein that is cleaved to form a mature, secreted protein. The N-terminus of the precursor protein shares characteristics with other surfactant proteins and is sometimes called chondrosurfactant protein although no biological activity has yet been defined for it. The C-terminus of the precursor protein contains a 25 kDa mature protein called leukocyte cell-derived chemotaxin-1 or chondromodulin-1. The mature protein promotes chondrocyte growth and inhibits angiogenesis. This gene is expressed in the avascular zone of prehypertrophic cartilage and its expression decreases during chondrocyte hypertrophy and vascular invasion. The mature protein likely plays a role in endochondral bone development by permitting cartilaginous anlagen to be vascularized and replaced by bone. It may be involved also in the broad control of tissue vascularization during development. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CNMD | NM_007015.3 | c.245A>G | p.Asn82Ser | missense_variant | 3/7 | ENST00000377962.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CNMD | ENST00000377962.8 | c.245A>G | p.Asn82Ser | missense_variant | 3/7 | 1 | NM_007015.3 | P4 | |
CNMD | ENST00000448904.6 | c.245A>G | p.Asn82Ser | missense_variant | 3/7 | 1 | A1 | ||
CNMD | ENST00000431550.1 | c.11A>G | p.Asn4Ser | missense_variant | 2/4 | 2 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
Cov.:
33
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251436Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135890
GnomAD3 exomes
AF:
AC:
1
AN:
251436
Hom.:
AF XY:
AC XY:
1
AN XY:
135890
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.00000342 AC: 5AN: 1461628Hom.: 0 Cov.: 30 AF XY: 0.00000550 AC XY: 4AN XY: 727128
GnomAD4 exome
AF:
AC:
5
AN:
1461628
Hom.:
Cov.:
30
AF XY:
AC XY:
4
AN XY:
727128
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? Cov.: 33
GnomAD4 genome
?
Cov.:
33
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 06, 2023 | The c.245A>G (p.N82S) alteration is located in exon 3 (coding exon 3) of the LECT1 gene. This alteration results from a A to G substitution at nucleotide position 245, causing the asparagine (N) at amino acid position 82 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Uncertain
Dann
Uncertain
Eigen
Uncertain
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Benign
D;D;T
M_CAP
Benign
T
MetaRNN
Uncertain
T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D;D
REVEL
Benign
Sift
Uncertain
D;D;D
Sift4G
Uncertain
D;D;.
Polyphen
D;D;.
Vest4
MutPred
Gain of catalytic residue at Y77 (P = 0.0012);Gain of catalytic residue at Y77 (P = 0.0012);.;
MVP
MPC
0.54
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at