Genetic Variant CLEC18A:p.Ala19Gly (chr16-69951422-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001370523.4(CLEC18A):c.56C>G(p.Ala19Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A19V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 0.000048 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CLEC18A
NM_001370523.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.101

Publications

1 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.07651222).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001370523.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CLEC18A	NM_001370523.4	MANE Select	c.56C>G	p.Ala19Gly	missense	Exon 1 of 12	NP_001357452.1	A5D8T8-1
CLEC18A	NM_001136214.4		c.56C>G	p.Ala19Gly	missense	Exon 2 of 13	NP_001129686.1	A5D8T8-1
CLEC18A	NM_001271197.3		c.56C>G	p.Ala19Gly	missense	Exon 2 of 13	NP_001258126.1	A5D8T8-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CLEC18A	ENST00000288040.11	TSL:1 MANE Select	c.56C>G	p.Ala19Gly	missense	Exon 1 of 12	ENSP00000288040.6	A5D8T8-1
CLEC18A	ENST00000393701.6	TSL:1	c.56C>G	p.Ala19Gly	missense	Exon 2 of 13	ENSP00000377304.2	A5D8T8-1
CLEC18A	ENST00000568461.5	TSL:1	c.56C>G	p.Ala19Gly	missense	Exon 2 of 13	ENSP00000454685.1	A5D8T8-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000295

AC:

AN:

67730

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000613

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000394

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000480

AC:

AN:

1459298

Hom.:

Cov.:

AF XY:

0.0000455

AC XY:

AN XY:

725976

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

33404

American (AMR)

AF:

0.00

AC:

AN:

44696

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26118

East Asian (EAS)

AF:

0.00

AC:

AN:

39688

South Asian (SAS)

AF:

0.00

AC:

AN:

86130

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53356

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4134

European-Non Finnish (NFE)

AF:

0.0000621

AC:

AN:

1111614

Other (OTH)

AF:

0.0000166

AC:

AN:

60158

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.287

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.091

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.72

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.015

Eigen

Benign

-0.75

Eigen_PC

Benign

-0.71

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.72

M_CAP

Benign

0.0028

MetaRNN

Benign

0.077

MetaSVM

Benign

-0.95

MutationAssessor

Benign

1.3

PhyloP100

-0.10

PrimateAI

Uncertain

0.65

PROVEAN

Benign

-1.0

REVEL

Benign

0.040

Sift

Benign

0.13

Sift4G

Benign

0.42

Polyphen

0.043

Vest4

0.16

MVP

0.11

MPC

2.1

ClinPred

0.056

GERP RS

1.6

PromoterAI

0.0036

Neutral

(source)

Varity_R

0.088

gMVP

0.24

Mutation Taster

=86/14

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over