12-8519045-C-G

Variant summary

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

The NM_080387.5(CLEC4D):​c.269C>G​(p.Ala90Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,824 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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. A90T) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

CLEC4D
NM_080387.5 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0330
Variant links:
Genes affected
CLEC4D (HGNC:14554): (C-type lectin domain family 4 member D) 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. 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=0.08562252).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CLEC4DNM_080387.5 linkc.269C>G p.Ala90Gly missense_variant Exon 4 of 6 ENST00000299665.3 NP_525126.2 Q8WXI8
CLEC4DXM_011520632.3 linkc.269C>G p.Ala90Gly missense_variant Exon 5 of 7 XP_011518934.1 Q8WXI8
CLEC4DXM_047428771.1 linkc.269C>G p.Ala90Gly missense_variant Exon 4 of 6 XP_047284727.1
CLEC4DXM_047428772.1 linkc.269C>G p.Ala90Gly missense_variant Exon 4 of 6 XP_047284728.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CLEC4DENST00000299665.3 linkc.269C>G p.Ala90Gly missense_variant Exon 4 of 6 1 NM_080387.5 ENSP00000299665.2 Q8WXI8
CLEC4DENST00000382064.6 linkc.269C>G p.Ala90Gly missense_variant Exon 5 of 6 3 ENSP00000371496.2 A6NHA5

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1461824
Hom.:
0
Cov.:
30
AF XY:
0.00000275
AC XY:
2
AN XY:
727206
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:
0.00000180
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000378
Asia WGS
AF:
0.000289
AC:
1
AN:
3478
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Mar 04, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.269C>G (p.A90G) alteration is located in exon 4 (coding exon 4) of the CLEC4D gene. This alteration results from a C to G substitution at nucleotide position 269, causing the alanine (A) at amino acid position 90 to be replaced by a glycine (G). 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
0.10
BayesDel_addAF
Benign
-0.30
T
BayesDel_noAF
Benign
-0.66
CADD
Benign
15
DANN
Benign
0.95
DEOGEN2
Benign
0.0065
.;T
Eigen
Benign
-0.85
Eigen_PC
Benign
-0.88
FATHMM_MKL
Benign
0.11
N
LIST_S2
Benign
0.062
T;T
M_CAP
Benign
0.0042
T
MetaRNN
Benign
0.086
T;T
MetaSVM
Benign
-0.99
T
MutationAssessor
Benign
1.8
.;L
PrimateAI
Benign
0.24
T
PROVEAN
Benign
-2.1
N;N
REVEL
Benign
0.042
Sift
Benign
0.14
T;T
Sift4G
Benign
0.32
T;T
Polyphen
0.0010
.;B
Vest4
0.28
MutPred
0.53
Loss of stability (P = 0.0527);Loss of stability (P = 0.0527);
MVP
0.15
MPC
0.031
ClinPred
0.064
T
GERP RS
0.47
Varity_R
0.22
gMVP
0.25

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs369634533; hg19: chr12-8671641; API