12-8518212-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_080387.5(CLEC4D):ā€‹c.170A>Gā€‹(p.Lys57Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000275 in 1,452,844 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/23 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.0000066 ( 0 hom., cov: 32)
Exomes š‘“: 0.0000023 ( 0 hom. )

Consequence

CLEC4D
NM_080387.5 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.245
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 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CLEC4DNM_080387.5 linkc.170A>G p.Lys57Arg missense_variant 3/6 ENST00000299665.3 NP_525126.2 Q8WXI8
CLEC4DXM_011520632.3 linkc.170A>G p.Lys57Arg missense_variant 4/7 XP_011518934.1 Q8WXI8
CLEC4DXM_047428771.1 linkc.170A>G p.Lys57Arg missense_variant 3/6 XP_047284727.1
CLEC4DXM_047428772.1 linkc.170A>G p.Lys57Arg missense_variant 3/6 XP_047284728.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CLEC4DENST00000299665.3 linkc.170A>G p.Lys57Arg missense_variant 3/61 NM_080387.5 ENSP00000299665.2 Q8WXI8
CLEC4DENST00000382064.6 linkc.170A>G p.Lys57Arg missense_variant 4/63 ENSP00000371496.2 A6NHA5

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152240
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000193
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000241
AC:
6
AN:
248656
Hom.:
0
AF XY:
0.0000223
AC XY:
3
AN XY:
134496
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000274
Gnomad SAS exome
AF:
0.0000332
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000231
AC:
3
AN:
1300486
Hom.:
0
Cov.:
21
AF XY:
0.00000153
AC XY:
1
AN XY:
654890
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000770
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000656
AC:
1
AN:
152358
Hom.:
0
Cov.:
32
AF XY:
0.0000134
AC XY:
1
AN XY:
74506
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
ExAC
AF:
0.0000330
AC:
4

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsSep 22, 2023The c.170A>G (p.K57R) alteration is located in exon 3 (coding exon 3) of the CLEC4D gene. This alteration results from a A to G substitution at nucleotide position 170, causing the lysine (K) at amino acid position 57 to be replaced by an arginine (R). 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
0.074
BayesDel_addAF
Benign
-0.54
T
BayesDel_noAF
Benign
-0.72
CADD
Benign
0.12
DANN
Benign
0.88
DEOGEN2
Benign
0.0048
.;T
Eigen
Benign
-1.1
Eigen_PC
Benign
-1.2
FATHMM_MKL
Benign
0.010
N
LIST_S2
Benign
0.38
T;T
M_CAP
Benign
0.0014
T
MetaRNN
Benign
0.029
T;T
MetaSVM
Benign
-0.91
T
MutationAssessor
Benign
1.9
.;L
PrimateAI
Benign
0.31
T
PROVEAN
Benign
-1.3
N;N
REVEL
Benign
0.016
Sift
Benign
0.29
T;T
Sift4G
Benign
0.43
T;T
Polyphen
0.011
.;B
Vest4
0.14
MVP
0.19
MPC
0.028
ClinPred
0.015
T
GERP RS
0.63
Varity_R
0.038
gMVP
0.28

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.32
Details are displayed if max score is > 0.2
DS_AL_spliceai
0.32
Position offset: -48

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: rs199672302; hg19: chr12-8670808; API