16-69952107-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PP3_Strong

The NM_001370523.4(CLEC18A):​c.197C>T​(p.Ala66Val) variant causes a missense change. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000022 ( 0 hom., cov: 12)
Exomes 𝑓: 0.000012 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

CLEC18A
NM_001370523.4 missense

Scores

3
10
6

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.51
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 Uncertain_significance. Variant got 4 ACMG points.

PP3
MetaRNN computational evidence supports a deleterious effect, 0.955

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CLEC18ANM_001370523.4 linkc.197C>T p.Ala66Val 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.197C>T p.Ala66Val missense_variant Exon 2 of 12 1 NM_001370523.4 ENSP00000288040.6 A5D8T8-1

Frequencies

GnomAD3 genomes
AF:
0.00
AC:
2
AN:
89044
Hom.:
0
Cov.:
12
FAILED QC
Gnomad AFR
AF:
0.0000913
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.0000124
AC:
6
AN:
485410
Hom.:
0
Cov.:
6
AF XY:
0.00000802
AC XY:
2
AN XY:
249312
show subpopulations
Gnomad4 AFR exome
AF:
0.000162
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000248
Gnomad4 FIN exome
AF:
0.0000261
Gnomad4 NFE exome
AF:
0.00000316
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.0000225
AC:
2
AN:
89044
Hom.:
0
Cov.:
12
AF XY:
0.0000485
AC XY:
2
AN XY:
41252
show subpopulations
Gnomad4 AFR
AF:
0.0000913
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:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000843
Hom.:
0

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Oct 04, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.197C>T (p.A66V) 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 197, causing the alanine (A) at amino acid position 66 to be replaced by a valine (V). 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
Uncertain
0.42
BayesDel_addAF
Benign
-0.073
T
BayesDel_noAF
Benign
-0.34
CADD
Pathogenic
28
DANN
Uncertain
1.0
DEOGEN2
Benign
0.14
T;T;T;T;.
Eigen
Uncertain
0.50
Eigen_PC
Uncertain
0.31
FATHMM_MKL
Uncertain
0.92
D
LIST_S2
Uncertain
0.88
D;.;.;.;D
M_CAP
Benign
0.068
D
MetaRNN
Pathogenic
0.95
D;D;D;D;D
MetaSVM
Benign
-0.49
T
MutationAssessor
Pathogenic
4.1
H;H;H;H;.
PrimateAI
Pathogenic
0.90
D
PROVEAN
Uncertain
-3.5
.;D;D;D;D
REVEL
Uncertain
0.35
Sift
Uncertain
0.0010
.;D;D;D;D
Sift4G
Uncertain
0.0040
D;D;D;D;D
Polyphen
1.0
D;D;D;D;D
Vest4
0.66
MutPred
0.92
Loss of disorder (P = 0.0533);Loss of disorder (P = 0.0533);Loss of disorder (P = 0.0533);Loss of disorder (P = 0.0533);Loss of disorder (P = 0.0533);
MVP
0.39
MPC
3.4
ClinPred
1.0
D
GERP RS
2.5
Varity_R
0.53
gMVP
0.54

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: rs1344888245; hg19: chr16-69986010; API