16-74412787-C-T

Variant summary

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

The NM_001385193.1(CLEC18B):​c.770G>A​(p.Gly257Asp) variant causes a missense change. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 41)
Exomes 𝑓: 0.000028 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

CLEC18B
NM_001385193.1 missense

Scores

4
11
4

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.19
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.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CLEC18BNM_001385193.1 linkc.770G>A p.Gly257Asp missense_variant Exon 6 of 12 ENST00000682950.1 NP_001372122.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CLEC18BENST00000682950.1 linkc.770G>A p.Gly257Asp missense_variant Exon 6 of 12 NM_001385193.1 ENSP00000507367.1 A0A804HJ60
CLEC18BENST00000339953.9 linkc.770G>A p.Gly257Asp missense_variant Exon 6 of 13 1 ENSP00000341051.5 Q6UXF7-1
CLEC18BENST00000425714.2 linkn.730G>A non_coding_transcript_exon_variant Exon 5 of 7 2
CLEC18BENST00000564842.1 linkn.13G>A non_coding_transcript_exon_variant Exon 1 of 3 4

Frequencies

GnomAD3 genomes
AF:
0.0000460
AC:
7
AN:
152218
Hom.:
0
Cov.:
41
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000458
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
GnomAD3 exomes
AF:
0.000173
AC:
43
AN:
248170
Hom.:
0
AF XY:
0.000171
AC XY:
23
AN XY:
134634
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00125
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.0000281
AC:
41
AN:
1459610
Hom.:
0
Cov.:
36
AF XY:
0.0000289
AC XY:
21
AN XY:
726096
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000917
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.0000460
AC:
7
AN:
152218
Hom.:
0
Cov.:
41
AF XY:
0.0000672
AC XY:
5
AN XY:
74352
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.000458
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
ExAC
AF:
0.000124
AC:
15

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Sep 27, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.770G>A (p.G257D) alteration is located in exon 6 (coding exon 6) of the CLEC18B gene. This alteration results from a G to A substitution at nucleotide position 770, causing the glycine (G) at amino acid position 257 to be replaced by an aspartic acid (D). 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
Pathogenic
0.88
BayesDel_addAF
Uncertain
0.069
T
BayesDel_noAF
Pathogenic
0.28
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.34
.;.;T;.
Eigen
Uncertain
0.30
Eigen_PC
Benign
0.22
FATHMM_MKL
Uncertain
0.97
D
LIST_S2
Uncertain
0.92
D;.;D;D
M_CAP
Pathogenic
0.42
D
MetaRNN
Uncertain
0.56
D;D;D;D
MetaSVM
Uncertain
0.39
D
MutationAssessor
Uncertain
2.3
.;.;M;.
PrimateAI
Uncertain
0.75
T
PROVEAN
Uncertain
-3.9
.;.;D;.
REVEL
Pathogenic
0.76
Sift
Uncertain
0.0020
.;.;D;.
Sift4G
Benign
0.081
T;T;T;T
Polyphen
1.0
.;.;D;.
Vest4
0.93
MutPred
0.48
Loss of catalytic residue at P253 (P = 0.1163);Loss of catalytic residue at P253 (P = 0.1163);Loss of catalytic residue at P253 (P = 0.1163);Loss of catalytic residue at P253 (P = 0.1163);
MVP
0.22
ClinPred
0.32
T
GERP RS
3.1
Varity_R
0.69
gMVP
0.82

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: rs759144388; hg19: chr16-74446685; API