rs1292647909

Variant names:

• chr16-69952086-G-A
• rs1292647909
• NM_001370523.4:c.176G>A

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PP3_Strong

The NM_001370523.4(CLEC18A):​c.176G>A​(p.Arg59His) variant causes a missense change. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 11)
  • Exomes 𝑓: 0.0000086 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CLEC18A NM_001370523.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.28
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.961

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLEC18A	NM_001370523.4	MANE Select	c.176G>A	p.Arg59His	missense	Exon 2 of 12	NP_001357452.1	A5D8T8-1
	CLEC18A	NM_001136214.4		c.176G>A	p.Arg59His	missense	Exon 3 of 13	NP_001129686.1	A5D8T8-1
	CLEC18A	NM_001271197.3		c.176G>A	p.Arg59His	missense	Exon 3 of 13	NP_001258126.1	A5D8T8-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLEC18A	ENST00000288040.11	TSL:1 MANE Select	c.176G>A	p.Arg59His	missense	Exon 2 of 12	ENSP00000288040.6	A5D8T8-1
	CLEC18A	ENST00000393701.6	TSL:1	c.176G>A	p.Arg59His	missense	Exon 3 of 13	ENSP00000377304.2	A5D8T8-1
	CLEC18A	ENST00000568461.5	TSL:1	c.176G>A	p.Arg59His	missense	Exon 3 of 13	ENSP00000454685.1	A5D8T8-1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 88150 Hom.: 0 Cov.: 11

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000859 AC: 5 AN: 582330 Hom.: 0 Cov.: 8 AF XY: 0.0000135 AC XY: 4 AN XY: 296840

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

African (AFR) AF: 0.00 AC: 0 AN: 14250

American (AMR) AF: 0.00 AC: 0 AN: 17282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13570

East Asian (EAS) AF: 0.0000381 AC: 1 AN: 26232

South Asian (SAS) AF: 0.0000649 AC: 3 AN: 46248

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40160

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2176

European-Non Finnish (NFE) AF: 0.00000254 AC: 1 AN: 393290

Other (OTH) AF: 0.00 AC: 0 AN: 29122

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0355984), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 88150 Hom.: 0 Cov.: 11 AF XY: 0.00 AC XY: 0 AN XY: 40560

African (AFR) AF: 0.00 AC: 0 AN: 22114

American (AMR) AF: 0.00 AC: 0 AN: 8170

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2418

East Asian (EAS) AF: 0.00 AC: 0 AN: 2350

South Asian (SAS) AF: 0.00 AC: 0 AN: 2344

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 4562

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 260

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 44198

Other (OTH) AF: 0.00 AC: 0 AN: 1206

Alfa AF: 0.00 Hom.: 0

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	Benign	0.32
BayesDel_addAF	Uncertain	0.048	T
BayesDel_noAF	Benign	-0.17
CADD	Pathogenic	27
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.23	T
Eigen	Uncertain	0.52
Eigen_PC	Uncertain	0.30
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.060	D
MetaRNN	Pathogenic	0.96	D
MetaSVM	Uncertain	-0.036	T
MutationAssessor	Pathogenic	4.9	H
PhyloP100		5.3
PrimateAI	Pathogenic	0.88	D
PROVEAN	Pathogenic	-4.5	D
REVEL	Uncertain	0.48
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.82
MutPred		0.89		Loss of MoRF binding (P = 0.0077)
MVP		0.74
MPC		4.2
ClinPred		1.0	D
GERP RS		2.5
PromoterAI		-0.091	Neutral
Varity_R		0.96
gMVP		0.78
Mutation Taster		=92/8	polymorphism

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

Other links and lift over

dbSNP: rs1292647909; hg19: chr16-69985989;