12-10075566-A-T

Variant summary

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

The NM_016511.4(CLEC1A):​c.481T>A​(p.Cys161Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000282 in 1,613,880 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 0.00012 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00030 ( 0 hom. )

Consequence

CLEC1A
NM_016511.4 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.42
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=0.12924811).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CLEC1ANM_016511.4 linkuse as main transcriptc.481T>A p.Cys161Ser missense_variant 4/6 ENST00000315330.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CLEC1AENST00000315330.8 linkuse as main transcriptc.481T>A p.Cys161Ser missense_variant 4/61 NM_016511.4 P1
CLEC1AENST00000457018.6 linkuse as main transcriptc.382T>A p.Cys128Ser missense_variant 3/52
CLEC1AENST00000420265.2 linkuse as main transcriptc.205T>A p.Cys69Ser missense_variant 2/42

Frequencies

GnomAD3 genomes
AF:
0.000118
AC:
18
AN:
152192
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000262
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:
0.000191
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000179
AC:
45
AN:
251198
Hom.:
0
AF XY:
0.000162
AC XY:
22
AN XY:
135762
show subpopulations
Gnomad AFR exome
AF:
0.0000616
Gnomad AMR exome
AF:
0.0000579
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.0000462
Gnomad NFE exome
AF:
0.000361
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000299
AC:
437
AN:
1461688
Hom.:
0
Cov.:
31
AF XY:
0.000303
AC XY:
220
AN XY:
727162
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.0000447
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.000131
Gnomad4 NFE exome
AF:
0.000377
Gnomad4 OTH exome
AF:
0.000132
GnomAD4 genome
AF:
0.000118
AC:
18
AN:
152192
Hom.:
0
Cov.:
32
AF XY:
0.000121
AC XY:
9
AN XY:
74360
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.000262
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000191
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000188
Hom.:
0
Bravo
AF:
0.000132
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000349
AC:
3
ExAC
AF:
0.000239
AC:
29
EpiCase
AF:
0.000218
EpiControl
AF:
0.000296

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 GeneticsAug 09, 2021The c.481T>A (p.C161S) alteration is located in exon 4 (coding exon 4) of the CLEC1A gene. This alteration results from a T to A substitution at nucleotide position 481, causing the cysteine (C) at amino acid position 161 to be replaced by a serine (S). 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
0.87
BayesDel_addAF
Benign
-0.24
T
BayesDel_noAF
Benign
-0.27
CADD
Benign
19
DANN
Benign
0.71
DEOGEN2
Benign
0.022
T;.;.
Eigen
Benign
-0.12
Eigen_PC
Benign
-0.042
FATHMM_MKL
Benign
0.51
D
LIST_S2
Benign
0.73
T;T;T
M_CAP
Benign
0.0026
T
MetaRNN
Benign
0.13
T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.71
N;.;.
MutationTaster
Benign
0.81
D;D;D
PrimateAI
Benign
0.45
T
PROVEAN
Benign
2.0
N;N;N
REVEL
Benign
0.23
Sift
Benign
1.0
T;T;T
Sift4G
Benign
0.94
T;T;T
Polyphen
0.29
B;D;D
Vest4
0.58
MutPred
0.74
Gain of disorder (P = 0.0051);.;.;
MVP
0.38
MPC
0.052
ClinPred
0.079
T
GERP RS
3.8
Varity_R
0.16
gMVP
0.51

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: rs141650672; hg19: chr12-10228165; API