16-69951422-C-T

Variant names:

• chr16-69951422-C-T
• rs1214758727
• NM_001370523.4:c.56C>T

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.56C>T​(p.Ala19Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A19S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CLEC18A NM_001370523.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.101
• Publications: 1 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=0.07123515).

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.56C>T	p.Ala19Val	missense	Exon 1 of 12	NP_001357452.1	A5D8T8-1
	CLEC18A	NM_001136214.4		c.56C>T	p.Ala19Val	missense	Exon 2 of 13	NP_001129686.1	A5D8T8-1
	CLEC18A	NM_001271197.3		c.56C>T	p.Ala19Val	missense	Exon 2 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.56C>T	p.Ala19Val	missense	Exon 1 of 12	ENSP00000288040.6	A5D8T8-1
	CLEC18A	ENST00000393701.6	TSL:1	c.56C>T	p.Ala19Val	missense	Exon 2 of 13	ENSP00000377304.2	A5D8T8-1
	CLEC18A	ENST00000568461.5	TSL:1	c.56C>T	p.Ala19Val	missense	Exon 2 of 13	ENSP00000454685.1	A5D8T8-1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 6.85e-7 AC: 1 AN: 1459316 Hom.: 0 Cov.: 37 AF XY: 0.00000138 AC XY: 1 AN XY: 725986

⚠️ 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: 33404

American (AMR) AF: 0.0000224 AC: 1 AN: 44696

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26118

East Asian (EAS) AF: 0.00 AC: 0 AN: 39688

South Asian (SAS) AF: 0.00 AC: 0 AN: 86130

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53356

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4134

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111628

Other (OTH) AF: 0.00 AC: 0 AN: 60162

⚠️ 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 Cov.: 34

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	0.10
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	15
DANN	Benign	0.97
DEOGEN2	Benign	0.017	T
Eigen	Benign	-0.74
Eigen_PC	Benign	-0.71
FATHMM_MKL	Benign	0.076	N
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.0027	T
MetaRNN	Benign	0.071	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.3	L
PhyloP100		-0.10
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.010
Sift	Benign	0.23	T
Sift4G	Benign	0.21	T
Polyphen		0.0010	B
Vest4		0.12
MutPred		0.45		Gain of catalytic residue at A19 (P = 0.2799)
MVP		0.092
MPC		1.9
ClinPred		0.12	T
GERP RS		1.6
PromoterAI		-0.010	Neutral
Varity_R		0.066
gMVP		0.29

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: rs1214758727; hg19: chr16-69985325;