NM_001385193.1:c.997G>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001385193.1(CLEC18B):​c.997G>T​(p.Val333Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000132 in 152,006 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 59)
Exomes 𝑓: 0.000090 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

CLEC18B
NM_001385193.1 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.806
Variant links:
Genes affected
CLEC18B (HGNC:33849): (C-type lectin domain family 18 member B) Predicted to enable polysaccharide binding activity. Predicted to be located in Golgi apparatus; endosome; and sarcoplasmic reticulum. Predicted to be active in extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

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=0.20893773).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CLEC18BNM_001385193.1 linkc.997G>T p.Val333Leu missense_variant Exon 9 of 12 ENST00000682950.1 NP_001372122.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CLEC18BENST00000682950.1 linkc.997G>T p.Val333Leu missense_variant Exon 9 of 12 NM_001385193.1 ENSP00000507367.1 A0A804HJ60
CLEC18BENST00000339953.9 linkc.997G>T p.Val333Leu missense_variant Exon 9 of 13 1 ENSP00000341051.5 Q6UXF7-1

Frequencies

GnomAD3 genomes
AF:
0.0000132
AC:
2
AN:
152006
Hom.:
0
Cov.:
59
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000609
AC:
15
AN:
246346
Hom.:
1
AF XY:
0.0000751
AC XY:
10
AN XY:
133168
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.000102
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000127
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.0000902
AC:
131
AN:
1451662
Hom.:
0
Cov.:
128
AF XY:
0.0000928
AC XY:
67
AN XY:
722228
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000897
Gnomad4 ASJ exome
AF:
0.000154
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000108
Gnomad4 OTH exome
AF:
0.0000667
GnomAD4 genome
AF:
0.0000132
AC:
2
AN:
152006
Hom.:
0
Cov.:
59
AF XY:
0.0000135
AC XY:
1
AN XY:
74262
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000963
Hom.:
0
ExAC
AF:
0.000108
AC:
13

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Feb 16, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.997G>T (p.V333L) alteration is located in exon 9 (coding exon 9) of the CLEC18B gene. This alteration results from a G to T substitution at nucleotide position 997, causing the valine (V) at amino acid position 333 to be replaced by a leucine (L). 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
0.13
BayesDel_addAF
Benign
-0.19
T
BayesDel_noAF
Benign
-0.51
CADD
Benign
16
DANN
Benign
0.97
DEOGEN2
Benign
0.0065
.;.;T
Eigen
Benign
-0.75
Eigen_PC
Benign
-0.65
FATHMM_MKL
Benign
0.30
N
LIST_S2
Uncertain
0.90
D;.;D
M_CAP
Benign
0.011
T
MetaRNN
Benign
0.21
T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.14
.;.;N
PrimateAI
Uncertain
0.54
T
PROVEAN
Benign
-0.81
.;.;N
REVEL
Benign
0.064
Sift
Benign
0.040
.;.;D
Sift4G
Benign
0.13
T;T;T
Polyphen
0.22
.;.;B
Vest4
0.20
MutPred
0.58
Loss of MoRF binding (P = 0.0934);Loss of MoRF binding (P = 0.0934);Loss of MoRF binding (P = 0.0934);
MVP
0.030
ClinPred
0.053
T
GERP RS
0.90
Varity_R
0.068
gMVP
0.18

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.030
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs765021041; hg19: chr16-74444920; API