16-69952103-C-T

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP4

The NM_001370523.4(CLEC18A):​c.193C>T​(p.Pro65Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000090 ( 0 hom., cov: 11)
Exomes 𝑓: 0.000073 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

CLEC18A
NM_001370523.4 missense

Scores

2
2
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.17
Variant links:
Genes affected
CLEC18A (HGNC:30388): (C-type lectin domain family 18 member A) This is one of three closely related paralogous genes on chromosome 16 encoding secreted proteins containing C-type lectin domains. These domains bind to carbohydrates in the presence of calcium, and may be involved in cell adhesion, immune response and apoptosis. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Sep 2012]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -1 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.32645696).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CLEC18ANM_001370523.4 linkc.193C>T p.Pro65Ser missense_variant Exon 2 of 12 ENST00000288040.11 NP_001357452.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CLEC18AENST00000288040.11 linkc.193C>T p.Pro65Ser missense_variant Exon 2 of 12 1 NM_001370523.4 ENSP00000288040.6 A5D8T8-1

Frequencies

GnomAD3 genomes
AF:
0.0000900
AC:
8
AN:
88900
Hom.:
0
Cov.:
11
show subpopulations
Gnomad AFR
AF:
0.0000912
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000425
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000112
Gnomad OTH
AF:
0.00
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.0000733
AC:
37
AN:
505016
Hom.:
0
Cov.:
6
AF XY:
0.0000965
AC XY:
25
AN XY:
259050
show subpopulations
Gnomad4 AFR exome
AF:
0.0000785
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000288
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000725
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000900
AC:
8
AN:
88900
Hom.:
0
Cov.:
11
AF XY:
0.0000486
AC XY:
2
AN XY:
41182
show subpopulations
Gnomad4 AFR
AF:
0.0000912
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000425
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000112
Gnomad4 OTH
AF:
0.00

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Jan 03, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.193C>T (p.P65S) alteration is located in exon 3 (coding exon 2) of the CLEC18A gene. This alteration results from a C to T substitution at nucleotide position 193, causing the proline (P) at amino acid position 65 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
0.11
BayesDel_addAF
Benign
-0.30
T
BayesDel_noAF
Benign
-0.67
CADD
Benign
19
DANN
Uncertain
1.0
DEOGEN2
Benign
0.016
T;T;T;T;.
Eigen
Benign
-0.36
Eigen_PC
Benign
-0.49
FATHMM_MKL
Benign
0.11
N
LIST_S2
Benign
0.79
T;.;.;.;T
M_CAP
Benign
0.0044
T
MetaRNN
Benign
0.33
T;T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Uncertain
2.3
M;M;M;M;.
PrimateAI
Pathogenic
0.87
D
PROVEAN
Pathogenic
-4.7
.;D;D;D;D
REVEL
Benign
0.090
Sift
Benign
0.088
.;T;T;T;T
Sift4G
Benign
0.12
T;T;T;T;T
Polyphen
0.96
D;D;D;D;P
Vest4
0.23
MutPred
0.73
Gain of MoRF binding (P = 0.0376);Gain of MoRF binding (P = 0.0376);Gain of MoRF binding (P = 0.0376);Gain of MoRF binding (P = 0.0376);Gain of MoRF binding (P = 0.0376);
MVP
0.27
MPC
2.1
ClinPred
0.88
D
GERP RS
0.096
Varity_R
0.14
gMVP
0.21

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

LitVar

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

Other links and lift over

dbSNP: rs1299024495; hg19: chr16-69986006; API