12-8539282-C-T

Position:

• chr12-8539282-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 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. 13/21 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

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]

CLEC4E (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.090341836).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLEC4E	NM_014358.4	c.155G>A	p.Cys52Tyr	missense_variant	3/6	ENST00000299663.8	NP_055173.1
CLEC4E	NM_001410969.1	c.155G>A	p.Cys52Tyr	missense_variant	3/5		NP_001397898.1
CLEC4E	XM_011520614.4	c.62G>A	p.Cys21Tyr	missense_variant	2/5		XP_011518916.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLEC4E	ENST00000299663.8	c.155G>A	p.Cys52Tyr	missense_variant	3/6	1	NM_014358.4	ENSP00000299663.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 09, 2024

The c.155G>A (p.C52Y) alteration is located in exon 3 (coding exon 3) of the CLEC4E gene. This alteration results from a G to A substitution at nucleotide position 155, causing the cysteine (C) at amino acid position 52 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

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;.;T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.029	N
LIST_S2	Benign	0.63	T;.;T
M_CAP	Benign	0.0020	T
MetaRNN	Benign	0.090	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.9	M;.;.
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Uncertain	0.52	T
PROVEAN	Pathogenic	-4.6	D;D;D
REVEL	Benign	0.049
Sift	Benign	0.37	T;T;T
Sift4G	Benign	1.0	T;T;T
Polyphen		0.011	B;.;.
Vest4		0.29
MutPred		0.42		Gain of disorder (P = 0.062);Gain of disorder (P = 0.062);Gain of disorder (P = 0.062);
MVP		0.067
MPC		0.11
ClinPred		0.081	T
GERP RS		2.1
Varity_R		0.096
gMVP		0.30

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

Publications

LitVar

Other links and lift over

dbSNP: rs1339096358; hg19: chr12-8691878;