16-69954398-C-G

Variant names:

• chr16-69954398-C-G
• rs765753592
• NM_001370523.4:c.281C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001370523.4(CLEC18A):​c.281C>G​(p.Pro94Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000435 in 1,610,128 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 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. P94L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 26)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: CLEC18A NM_001370523.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.952
• Publications: 4 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18228662).

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.281C>G	p.Pro94Arg	missense	Exon 3 of 12	NP_001357452.1	A5D8T8-1
	CLEC18A	NM_001136214.4		c.281C>G	p.Pro94Arg	missense	Exon 4 of 13	NP_001129686.1	A5D8T8-1
	CLEC18A	NM_001271197.3		c.281C>G	p.Pro94Arg	missense	Exon 4 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.281C>G	p.Pro94Arg	missense	Exon 3 of 12	ENSP00000288040.6	A5D8T8-1
	CLEC18A	ENST00000393701.6	TSL:1	c.281C>G	p.Pro94Arg	missense	Exon 4 of 13	ENSP00000377304.2	A5D8T8-1
	CLEC18A	ENST00000568461.5	TSL:1	c.281C>G	p.Pro94Arg	missense	Exon 4 of 13	ENSP00000454685.1	A5D8T8-1

Frequencies

GnomAD3 genomes AF: 0.0000133 AC: 2 AN: 150214 Hom.: 0 Cov.: 26

Gnomad AFR AF: 0.0000483

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

GnomAD2 exomes AF: 0.00000402 AC: 1 AN: 248604 AF XY: 0.00

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1459914 Hom.: 0 Cov.: 71 AF XY: 0.00000138 AC XY: 1 AN XY: 726320

African (AFR) AF: 0.0000897 AC: 3 AN: 33456

American (AMR) AF: 0.0000224 AC: 1 AN: 44698

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26108

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 86128

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52922

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4978

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111624

Other (OTH) AF: 0.0000166 AC: 1 AN: 60300

GnomAD4 genome AF: 0.0000133 AC: 2 AN: 150214 Hom.: 0 Cov.: 26 AF XY: 0.0000137 AC XY: 1 AN XY: 73160

African (AFR) AF: 0.0000483 AC: 2 AN: 41386

American (AMR) AF: 0.00 AC: 0 AN: 14964

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3446

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4744

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10140

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67074

Other (OTH) AF: 0.00 AC: 0 AN: 2060

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.080
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	12
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0076	T
Eigen	Benign	-0.61
Eigen_PC	Benign	-0.84
FATHMM_MKL	Benign	0.021	N
LIST_S2	Benign	0.57	T
M_CAP	Benign	0.0025	T
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		-0.95
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.033
Sift	Benign	0.079	T
Sift4G	Benign	0.23	T
Polyphen		0.91	P
Vest4		0.21
MutPred		0.41		Gain of MoRF binding (P = 0.0015)
MVP		0.25
MPC		0.53
ClinPred		0.31	T
GERP RS		0.95
Varity_R		0.040
gMVP		0.16
Mutation Taster		=89/11	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: rs765753592; hg19: chr16-69988301;