chr12-8539282-C-T

Variant names:

• chr12-8539282-C-T
• rs1339096358
• NM_014358.4:c.155G>A

Variant summary

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

The NM_014358.4(CLEC4E):​c.155G>A​(p.Cys52Tyr) 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. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CLEC4E NM_014358.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.694
• Publications: 0 publications found

Genes affected

CLEC4E (HGNC:14555): (C-type lectin domain family 4 member E) This gene encodes a member of the C-type lectin/C-type lectin-like domain (CTL/CTLD) superfamily. Members of this family share a common protein fold and have diverse functions, such as cell adhesion, cell-cell signalling, glycoprotein turnover, and roles in inflammation and immune response. The encoded type II transmembrane protein is a downstream target of CCAAT/enhancer binding protein (C/EBP), beta (CEBPB) and may play a role in inflammation. Alternative splice variants have been described but their full-length sequence has not been determined. This gene is closely linked to other CTL/CTLD superfamily members on chromosome 12p13 in the natural killer gene complex region. [provided by RefSeq, Jul 2008]

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=0.090341836).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014358.4. 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
	CLEC4E	NM_014358.4	MANE Select	c.155G>A	p.Cys52Tyr	missense	Exon 3 of 6	NP_055173.1	Q9ULY5
	CLEC4E	NM_001410969.1		c.155G>A	p.Cys52Tyr	missense	Exon 3 of 5	NP_001397898.1	F5H5X7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLEC4E	ENST00000299663.8	TSL:1 MANE Select	c.155G>A	p.Cys52Tyr	missense	Exon 3 of 6	ENSP00000299663.3	Q9ULY5
	CLEC4E	ENST00000545274.5	TSL:3	c.155G>A	p.Cys52Tyr	missense	Exon 3 of 5	ENSP00000443034.1	F5H5X7
	CLEC4E	ENST00000446457.6	TSL:3	c.155G>A	p.Cys52Tyr	missense	Exon 3 of 4	ENSP00000387737.2	F8WFA1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

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	0.098
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	13
DANN	Benign	0.92
DEOGEN2	Benign	0.21	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.029	N
LIST_S2	Benign	0.63	T
M_CAP	Benign	0.0020	T
MetaRNN	Benign	0.090	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.9	M
PhyloP100		0.69
PrimateAI	Uncertain	0.52	T
PROVEAN	Pathogenic	-4.6	D
REVEL	Benign	0.049
Sift	Benign	0.37	T
Sift4G	Benign	1.0	T
Polyphen		0.011	B
Vest4		0.29
MutPred		0.42		Gain of disorder (P = 0.062)
MVP		0.067
MPC		0.11
ClinPred		0.081	T
GERP RS		2.1
PromoterAI		0.0062	Neutral
Varity_R		0.096
gMVP		0.30
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: rs1339096358; hg19: chr12-8691878;