NM_001385193.1:c.593A>G

Variant names:

• chr16-74413120-T-C
• rs369764401
• NM_001385193.1:c.593A>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PP3_Moderate

The NM_001385193.1(CLEC18B):​c.593A>G​(p.Tyr198Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000985 in 152,268 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000099 (0 hom., cov: 42)
  • Exomes 𝑓: 0.00016 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CLEC18B NM_001385193.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.74
• Publications: 1 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.915

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLEC18B	NM_001385193.1	MANE Select	c.593A>G	p.Tyr198Cys	missense	Exon 5 of 12	NP_001372122.1	A0A804HJ60
	CLEC18B	NM_001011880.3		c.593A>G	p.Tyr198Cys	missense	Exon 5 of 13	NP_001011880.2	Q6UXF7-1
	CLEC18B	NM_001385192.1		c.593A>G	p.Tyr198Cys	missense	Exon 6 of 13	NP_001372121.1	A0A804HJ60

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLEC18B	ENST00000682950.1	MANE Select	c.593A>G	p.Tyr198Cys	missense	Exon 5 of 12	ENSP00000507367.1	A0A804HJ60
	CLEC18B	ENST00000339953.9	TSL:1	c.593A>G	p.Tyr198Cys	missense	Exon 5 of 13	ENSP00000341051.5	Q6UXF7-1
	CLEC18B	ENST00000890001.1		c.593A>G	p.Tyr198Cys	missense	Exon 6 of 13	ENSP00000560060.1

Frequencies

GnomAD3 genomes AF: 0.0000985 AC: 15 AN: 152268 Hom.: 0 Cov.: 42

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

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: 0.000176

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.0000518 AC: 13 AN: 251124 AF XY: 0.0000368

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000970

Gnomad OTH exome AF: 0.000163

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000156 AC: 227 AN: 1459414 Hom.: 0 Cov.: 38 AF XY: 0.000143 AC XY: 104 AN XY: 726016

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

African (AFR) AF: 0.0000299 AC: 1 AN: 33402

American (AMR) AF: 0.0000224 AC: 1 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86164

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4140

European-Non Finnish (NFE) AF: 0.000186 AC: 207 AN: 1111554

Other (OTH) AF: 0.000282 AC: 17 AN: 60188

⚠️ 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.

GnomAD4 genome AF: 0.0000985 AC: 15 AN: 152268 Hom.: 0 Cov.: 42 AF XY: 0.0000941 AC XY: 7 AN XY: 74392

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

African (AFR) AF: 0.0000241 AC: 1 AN: 41480

American (AMR) AF: 0.0000654 AC: 1 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5204

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000176 AC: 12 AN: 68034

Other (OTH) AF: 0.000478 AC: 1 AN: 2094

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.0000959 Hom.: 0

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.0000494 AC: 6

EpiCase AF: 0.000109

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.86
BayesDel_addAF	Benign	-0.097	T
BayesDel_noAF	Benign	-0.16
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.51	D
Eigen	Uncertain	0.33
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.019	T
MetaRNN	Pathogenic	0.91	D
MetaSVM	Benign	-0.91	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		4.7
PrimateAI	Uncertain	0.76	T
PROVEAN	Pathogenic	-8.0	D
REVEL	Uncertain	0.43
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.039	D
Polyphen		1.0	D
Vest4		0.94
MVP		0.13
ClinPred		0.87	D
GERP RS		3.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.81
gMVP		0.83
Mutation Taster		=80/20	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs369764401; hg19: chr16-74447018;