12-10098874-C-A

Variant summary

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

The NM_016511.4(CLEC1A):​c.49G>T​(p.Asp17Tyr) 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: 31)

Consequence

CLEC1A
NM_016511.4 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.13
Variant links:
Genes affected
CLEC1A (HGNC:24355): (C-type lectin domain family 1 member A) 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 signaling, glycoprotein turnover, and roles in inflammation and immune response. The encoded protein may play a role in regulating dendritic cell function. This gene is closely linked to other CTL/CTLD superfamily members on chromosome 12p13 in the natural killer gene complex region. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014]

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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=0.18650639).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CLEC1ANM_016511.4 linkuse as main transcriptc.49G>T p.Asp17Tyr missense_variant 1/6 ENST00000315330.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CLEC1AENST00000315330.8 linkuse as main transcriptc.49G>T p.Asp17Tyr missense_variant 1/61 NM_016511.4 P1

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
Cov.:
33
GnomAD4 genome
Cov.:
31

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 GeneticsDec 09, 2023The c.49G>T (p.D17Y) alteration is located in exon 1 (coding exon 1) of the CLEC1A gene. This alteration results from a G to T substitution at nucleotide position 49, causing the aspartic acid (D) at amino acid position 17 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
0.093
BayesDel_addAF
Benign
-0.096
T
BayesDel_noAF
Benign
-0.38
CADD
Uncertain
24
DANN
Uncertain
0.99
DEOGEN2
Benign
0.0025
T;.;.;.
Eigen
Benign
-0.031
Eigen_PC
Benign
0.054
FATHMM_MKL
Benign
0.46
N
LIST_S2
Benign
0.86
D;D;D;T
M_CAP
Benign
0.0044
T
MetaRNN
Benign
0.19
T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.56
N;.;.;.
MutationTaster
Benign
0.85
N;N;N
PrimateAI
Benign
0.37
T
PROVEAN
Benign
3.1
N;N;N;N
REVEL
Benign
0.13
Sift
Benign
0.13
T;T;T;D
Sift4G
Benign
0.18
T;D;D;.
Polyphen
0.92
P;P;P;.
Vest4
0.59
MutPred
0.40
Gain of phosphorylation at D17 (P = 6e-04);Gain of phosphorylation at D17 (P = 6e-04);Gain of phosphorylation at D17 (P = 6e-04);Gain of phosphorylation at D17 (P = 6e-04);
MVP
0.67
MPC
0.27
ClinPred
0.82
D
GERP RS
4.6
Varity_R
0.082
gMVP
0.49

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-10251473; API