rs762109492

Variant names:

• chr16-74412178-C-G
• rs762109492
• NM_001385193.1:c.853G>C

Your query was ambiguous. Multiple possible variants found:

• chr16-74412178-C-G
• chr16-74412178-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001385193.1(CLEC18B):​c.853G>C​(p.Gly285Arg) 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. G285S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 37)
• Consequence: CLEC18B NM_001385193.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.54

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.808

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLEC18B	NM_001385193.1	c.853G>C	p.Gly285Arg	missense_variant	Exon 7 of 12	ENST00000682950.1	NP_001372122.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLEC18B	ENST00000682950.1	c.853G>C	p.Gly285Arg	missense_variant	Exon 7 of 12		NM_001385193.1	ENSP00000507367.1
CLEC18B	ENST00000339953.9	c.853G>C	p.Gly285Arg	missense_variant	Exon 7 of 13	1		ENSP00000341051.5
CLEC18B	ENST00000425714.2	n.897G>C		non_coding_transcript_exon_variant	Exon 7 of 7	2
CLEC18B	ENST00000564842.1	n.96G>C		non_coding_transcript_exon_variant	Exon 2 of 3	4

Frequencies

GnomAD3 genomes Cov.: 37

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 37

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.59
BayesDel_addAF	Benign	-0.041	T
BayesDel_noAF	Benign	-0.30
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.15	.;.;T;.
Eigen	Uncertain	0.30
Eigen_PC	Benign	0.21
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.94	D;.;D;D
M_CAP	Uncertain	0.12	D
MetaRNN	Pathogenic	0.81	D;D;D;D
MetaSVM	Benign	-0.92	T
MutationAssessor	Uncertain	2.5	.;.;M;.
PrimateAI	Uncertain	0.71	T
PROVEAN	Uncertain	-3.5	.;.;D;.
REVEL	Uncertain	0.33
Sift	Uncertain	0.0020	.;.;D;.
Sift4G	Pathogenic	0.0	D;D;D;D
Polyphen		1.0	.;.;D;.
Vest4		0.71
MutPred		0.61		Loss of catalytic residue at I284 (P = 0.1663);Loss of catalytic residue at I284 (P = 0.1663);Loss of catalytic residue at I284 (P = 0.1663);Loss of catalytic residue at I284 (P = 0.1663);
MVP		0.12
ClinPred		0.99	D
GERP RS		3.3
Varity_R		0.57
gMVP		0.64

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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

Other links and lift over

dbSNP: rs762109492; hg19: chr16-74446076;