chr13-52703719-T-G
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_007015.3(CNMD):c.881A>C(p.Gln294Pro) variant causes a missense change. The variant allele was found at a frequency of 0.00109 in 1,613,524 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00070 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0011 ( 1 hom. )
Consequence
CNMD
NM_007015.3 missense
NM_007015.3 missense
Scores
1
6
10
Clinical Significance
Conservation
PhyloP100: 4.72
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 0 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.12924492).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CNMD | NM_007015.3 | c.881A>C | p.Gln294Pro | missense_variant | 7/7 | ENST00000377962.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CNMD | ENST00000377962.8 | c.881A>C | p.Gln294Pro | missense_variant | 7/7 | 1 | NM_007015.3 | P4 | |
CNMD | ENST00000448904.6 | c.878A>C | p.Gln293Pro | missense_variant | 7/7 | 1 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.000703 AC: 107AN: 152176Hom.: 0 Cov.: 33
GnomAD3 genomes
?
AF:
AC:
107
AN:
152176
Hom.:
Cov.:
33
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.000462 AC: 116AN: 251166Hom.: 0 AF XY: 0.000420 AC XY: 57AN XY: 135742
GnomAD3 exomes
AF:
AC:
116
AN:
251166
Hom.:
AF XY:
AC XY:
57
AN XY:
135742
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: 0.00113 AC: 1653AN: 1461230Hom.: 1 Cov.: 31 AF XY: 0.00108 AC XY: 786AN XY: 726932
GnomAD4 exome
AF:
AC:
1653
AN:
1461230
Hom.:
Cov.:
31
AF XY:
AC XY:
786
AN XY:
726932
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 ? AF: 0.000703 AC: 107AN: 152294Hom.: 0 Cov.: 33 AF XY: 0.000577 AC XY: 43AN XY: 74490
GnomAD4 genome
?
AF:
AC:
107
AN:
152294
Hom.:
Cov.:
33
AF XY:
AC XY:
43
AN XY:
74490
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
TwinsUK
AF:
AC:
9
ALSPAC
AF:
AC:
5
ESP6500AA
AF:
AC:
0
ESP6500EA
AF:
AC:
8
ExAC
?
AF:
AC:
55
Asia WGS
AF:
AC:
1
AN:
3478
EpiCase
AF:
EpiControl
AF:
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 | Aug 01, 2022 | The c.881A>C (p.Q294P) alteration is located in exon 7 (coding exon 7) of the LECT1 gene. This alteration results from a A to C substitution at nucleotide position 881, causing the glutamine (Q) at amino acid position 294 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Pathogenic
Dann
Uncertain
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Uncertain
D;D
Sift4G
Uncertain
D;D
Polyphen
B;B
Vest4
MVP
MPC
0.67
ClinPred
T
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