Genetic Variant NM_001385193.1:c.439T>G (chr16-74418076-A-C) – ACMG Classification: Likely_pathogenic (6 pts)

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_001385193.1(CLEC18B):c.439T>G(p.Cys147Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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. C147R) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CLEC18B
NM_001385193.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.87

Publications

0 publications found

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]

CLEC18B links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.968

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001385193.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CLEC18B	NM_001385193.1	MANE Select	c.439T>G	p.Cys147Gly	missense	Exon 3 of 12	NP_001372122.1	A0A804HJ60
CLEC18B	NM_001011880.3		c.439T>G	p.Cys147Gly	missense	Exon 3 of 13	NP_001011880.2	Q6UXF7-1
CLEC18B	NM_001385192.1		c.439T>G	p.Cys147Gly	missense	Exon 4 of 13	NP_001372121.1	A0A804HJ60

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CLEC18B	ENST00000682950.1	MANE Select	c.439T>G	p.Cys147Gly	missense	Exon 3 of 12	ENSP00000507367.1	A0A804HJ60
CLEC18B	ENST00000339953.9	TSL:1	c.439T>G	p.Cys147Gly	missense	Exon 3 of 13	ENSP00000341051.5	Q6UXF7-1
CLEC18B	ENST00000890001.1		c.439T>G	p.Cys147Gly	missense	Exon 4 of 13	ENSP00000560060.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

192754

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS 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: AC0;AS_VQSR

AF:

0.00

AC:

AN:

1442696

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

717168

African (AFR)

AF:

0.00

AC:

AN:

32796

American (AMR)

AF:

0.00

AC:

AN:

37708

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25612

East Asian (EAS)

AF:

0.00

AC:

AN:

39194

South Asian (SAS)

AF:

0.00

AC:

AN:

83970

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52494

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5368

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1105776

Other (OTH)

AF:

0.00

AC:

AN:

59778

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.78

BayesDel_addAF

Pathogenic

0.23

BayesDel_noAF

Uncertain

0.10

CADD

Uncertain

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.21

Eigen

Uncertain

0.62

Eigen_PC

Uncertain

0.49

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.86

M_CAP

Benign

0.050

MetaRNN

Pathogenic

0.97

MetaSVM

Benign

-0.97

MutationAssessor

Pathogenic

4.7

PhyloP100

6.9

PrimateAI

Uncertain

0.76

PROVEAN

Pathogenic

-9.7

REVEL

Uncertain

0.46

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

0.96

Vest4

0.94

MutPred

0.77

Gain of disorder (P = 0.0193)

MVP

0.14

ClinPred

1.0

GERP RS

3.6

Varity_R

0.94

gMVP

0.93

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over