12-10073406-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_016511.4(CLEC1A):ā€‹c.549T>Gā€‹(p.Phe183Leu) 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 1,460,054 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 0.0000014 ( 0 hom. )

Consequence

CLEC1A
NM_016511.4 missense

Scores

2
9
8

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.74
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 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.746

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CLEC1ANM_016511.4 linkuse as main transcriptc.549T>G p.Phe183Leu missense_variant 5/6 ENST00000315330.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CLEC1AENST00000315330.8 linkuse as main transcriptc.549T>G p.Phe183Leu missense_variant 5/61 NM_016511.4 P1
CLEC1AENST00000457018.6 linkuse as main transcriptc.450T>G p.Phe150Leu missense_variant 4/52
CLEC1AENST00000420265.2 linkuse as main transcriptc.273T>G p.Phe91Leu missense_variant 3/42

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000399
AC:
1
AN:
250396
Hom.:
0
AF XY:
0.00000739
AC XY:
1
AN XY:
135356
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000883
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1460054
Hom.:
0
Cov.:
29
AF XY:
0.00000138
AC XY:
1
AN XY:
726400
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:
9.00e-7
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
Cov.:
32
ExAC
AF:
0.00000824
AC:
1

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 GeneticsNov 10, 2022The c.549T>G (p.F183L) alteration is located in exon 5 (coding exon 5) of the CLEC1A gene. This alteration results from a T to G substitution at nucleotide position 549, causing the phenylalanine (F) at amino acid position 183 to be replaced by a leucine (L). 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
Pathogenic
0.97
BayesDel_addAF
Uncertain
0.11
D
BayesDel_noAF
Uncertain
-0.070
CADD
Benign
22
DANN
Uncertain
0.99
DEOGEN2
Benign
0.090
T;.;.
Eigen
Uncertain
0.30
Eigen_PC
Uncertain
0.26
FATHMM_MKL
Benign
0.74
D
LIST_S2
Benign
0.77
T;T;T
M_CAP
Benign
0.017
T
MetaRNN
Pathogenic
0.75
D;D;D
MetaSVM
Benign
-0.70
T
MutationAssessor
Uncertain
2.6
M;.;.
MutationTaster
Benign
0.63
D;D;D
PrimateAI
Uncertain
0.56
T
PROVEAN
Uncertain
-4.1
D;D;D
REVEL
Benign
0.20
Sift
Benign
0.080
T;T;T
Sift4G
Uncertain
0.042
D;T;T
Polyphen
0.94
P;P;P
Vest4
0.62
MutPred
0.74
Gain of disorder (P = 0.1105);.;.;
MVP
0.42
MPC
0.16
ClinPred
0.97
D
GERP RS
4.2
Varity_R
0.29
gMVP
0.68

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: rs778494710; hg19: chr12-10226005; API