12-8539944-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_014358.4(CLEC4E):​c.41G>C​(p.Arg14Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000417 in 1,439,624 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
Exomes 𝑓: 0.0000042 ( 0 hom. )

Consequence

CLEC4E
NM_014358.4 missense

Scores

4
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.313
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.11666149).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CLEC4ENM_014358.4 linkc.41G>C p.Arg14Thr missense_variant Exon 2 of 6 ENST00000299663.8 NP_055173.1 Q9ULY5
CLEC4ENM_001410969.1 linkc.41G>C p.Arg14Thr missense_variant Exon 2 of 5 NP_001397898.1
CLEC4EXM_011520614.4 linkc.38-638G>C intron_variant Intron 1 of 4 XP_011518916.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CLEC4EENST00000299663.8 linkc.41G>C p.Arg14Thr missense_variant Exon 2 of 6 1 NM_014358.4 ENSP00000299663.3 Q9ULY5

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000417
AC:
6
AN:
1439624
Hom.:
0
Cov.:
26
AF XY:
0.00000418
AC XY:
3
AN XY:
717610
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000550
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Dec 31, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.41G>C (p.R14T) alteration is located in exon 2 (coding exon 2) of the CLEC4E gene. This alteration results from a G to C substitution at nucleotide position 41, causing the arginine (R) at amino acid position 14 to be replaced by a threonine (T). 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
0.082
BayesDel_addAF
Benign
-0.18
T
BayesDel_noAF
Benign
-0.50
CADD
Benign
7.8
DANN
Benign
0.95
DEOGEN2
Benign
0.15
T;.;T
Eigen
Benign
-0.77
Eigen_PC
Benign
-0.90
FATHMM_MKL
Benign
0.038
N
LIST_S2
Benign
0.67
T;.;T
M_CAP
Benign
0.0053
T
MetaRNN
Benign
0.12
T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Uncertain
2.5
M;.;.
PrimateAI
Benign
0.24
T
PROVEAN
Uncertain
-2.5
N;D;N
REVEL
Benign
0.054
Sift
Uncertain
0.010
D;D;D
Sift4G
Uncertain
0.015
D;D;D
Polyphen
0.27
B;.;.
Vest4
0.25
MutPred
0.39
Loss of phosphorylation at T12 (P = 0.0683);Loss of phosphorylation at T12 (P = 0.0683);Loss of phosphorylation at T12 (P = 0.0683);
MVP
0.30
MPC
0.094
ClinPred
0.32
T
GERP RS
0.034
Varity_R
0.10
gMVP
0.34

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.16
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-8692540; API