chr12-10098832-G-A

Variant summary

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

The NM_016511.4(CLEC1A):​c.91C>T​(p.Arg31Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000044 in 1,613,172 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000044 ( 0 hom. )

Consequence

CLEC1A
NM_016511.4 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.165
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]

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=0.07272136).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CLEC1ANM_016511.4 linkuse as main transcriptc.91C>T p.Arg31Trp missense_variant 1/6 ENST00000315330.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CLEC1AENST00000315330.8 linkuse as main transcriptc.91C>T p.Arg31Trp missense_variant 1/61 NM_016511.4 P1

Frequencies

GnomAD3 genomes
AF:
0.0000460
AC:
7
AN:
152124
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000966
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.0000440
AC:
11
AN:
250132
Hom.:
0
AF XY:
0.0000296
AC XY:
4
AN XY:
135168
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:
0.0000329
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000884
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000438
AC:
64
AN:
1461048
Hom.:
0
Cov.:
29
AF XY:
0.0000358
AC XY:
26
AN XY:
726740
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000448
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000101
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000513
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000460
AC:
7
AN:
152124
Hom.:
0
Cov.:
32
AF XY:
0.0000269
AC XY:
2
AN XY:
74310
show subpopulations
Gnomad4 AFR
AF:
0.0000966
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.000478
Alfa
AF:
0.0000579
Hom.:
0
Bravo
AF:
0.0000227
ExAC
AF:
0.0000659
AC:
8
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

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 01, 2021The c.91C>T (p.R31W) alteration is located in exon 1 (coding exon 1) of the CLEC1A gene. This alteration results from a C to T substitution at nucleotide position 91, causing the arginine (R) at amino acid position 31 to be replaced by a tryptophan (W). 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
-0.33
T
BayesDel_noAF
Benign
-0.52
CADD
Benign
15
DANN
Uncertain
0.99
DEOGEN2
Benign
0.068
T;.;.;.
Eigen
Benign
-0.82
Eigen_PC
Benign
-0.89
FATHMM_MKL
Benign
0.054
N
LIST_S2
Benign
0.79
T;T;T;T
M_CAP
Benign
0.0072
T
MetaRNN
Benign
0.073
T;T;T;T
MetaSVM
Benign
-0.99
T
MutationAssessor
Benign
1.7
L;.;.;.
MutationTaster
Benign
1.0
N;N;N
PrimateAI
Benign
0.20
T
PROVEAN
Benign
-2.3
N;N;N;N
REVEL
Benign
0.035
Sift
Benign
0.039
D;T;T;T
Sift4G
Uncertain
0.0090
D;D;D;.
Polyphen
0.013
B;B;B;.
Vest4
0.14
MVP
0.53
MPC
0.037
ClinPred
0.11
T
GERP RS
0.043
Varity_R
0.052
gMVP
0.27

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: rs753560979; hg19: chr12-10251431; API