Genetic Variant CLEC18A:p.Glu47Gly (chr16-69952050-A-G) – ACMG Classification: Likely_benign (-1 pts)

Variant summary

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

The NM_001370523.4(CLEC18A):c.140A>G(p.Glu47Gly) variant causes a missense change. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000034 ( 0 hom., cov: 11)

Exomes 𝑓: 0.000022 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CLEC18A
NM_001370523.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.83

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]

CLEC18A links:

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=0.39036584).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLEC18A	NM_001370523.4 link	c.140A>G	p.Glu47Gly	missense_variant	Exon 2 of 12	ENST00000288040.11	NP_001357452.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLEC18A	ENST00000288040.11 link	c.140A>G	p.Glu47Gly	missense_variant	Exon 2 of 12	1	NM_001370523.4	ENSP00000288040.6		A5D8T8-1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

88294

Hom.:

Cov.:

FAILED QC

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:

0.0000680

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000217

AC:

AN:

507316

Hom.:

Cov.:

AF XY:

0.0000191

AC XY:

AN XY:

261750

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

0.0000339

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000340

AC:

AN:

88294

Hom.:

Cov.:

AF XY:

0.0000249

AC XY:

AN XY:

40128

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:

0.0000680

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

Nov 17, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.140A>G (p.E47G) alteration is located in exon 3 (coding exon 2) of the CLEC18A gene. This alteration results from a A to G substitution at nucleotide position 140, causing the glutamic acid (E) at amino acid position 47 to be replaced by a glycine (G). 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

0.20

BayesDel_addAF

Benign

-0.097

BayesDel_noAF

Benign

-0.38

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.075

T;T;T;T;.

Eigen

Benign

0.10

Eigen_PC

Benign

0.0070

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.81

T;.;.;.;T

M_CAP

Benign

0.019

MetaRNN

Benign

0.39

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.3

M;M;M;M;.

PrimateAI

Uncertain

0.71

PROVEAN

Pathogenic

-5.5

.;D;D;D;D

REVEL

Benign

0.18

Sift

Uncertain

0.0020

.;D;D;D;D

Sift4G

Uncertain

0.0050

D;D;D;D;D

Polyphen

1.0

D;D;D;D;D

Vest4

0.38

MutPred

0.44

Gain of MoRF binding (P = 0.023);Gain of MoRF binding (P = 0.023);Gain of MoRF binding (P = 0.023);Gain of MoRF binding (P = 0.023);Gain of MoRF binding (P = 0.023);

MVP

0.43

MPC

3.4

ClinPred

0.99

GERP RS

2.5

Varity_R

0.58

gMVP

0.56

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over