17-7076919-C-T

Variant summary

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

The NM_001330070.2(CLEC10A):​c.253G>A​(p.Ala85Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000397 in 1,613,874 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 0.000026 ( 0 hom., cov: 28)
Exomes 𝑓: 0.000041 ( 0 hom. )

Consequence

CLEC10A
NM_001330070.2 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0690
Variant links:
Genes affected
CLEC10A (HGNC:16916): (C-type lectin domain containing 10A) 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. The encoded type 2 transmembrane protein may function as a cell surface antigen. Two transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Jul 2008]

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=0.11393851).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CLEC10ANM_001330070.2 linkuse as main transcriptc.253G>A p.Ala85Thr missense_variant 4/9 ENST00000416562.7 NP_001316999.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CLEC10AENST00000416562.7 linkuse as main transcriptc.253G>A p.Ala85Thr missense_variant 4/95 NM_001330070.2 ENSP00000414938 A2
CLEC10AENST00000254868.8 linkuse as main transcriptc.253G>A p.Ala85Thr missense_variant 4/91 ENSP00000254868 Q8IUN9-1
CLEC10AENST00000571664.1 linkuse as main transcriptc.253G>A p.Ala85Thr missense_variant 4/91 ENSP00000460252 P4Q8IUN9-2
CLEC10AENST00000576617.5 linkuse as main transcriptc.253G>A p.Ala85Thr missense_variant 4/71 ENSP00000458728 Q8IUN9-3

Frequencies

GnomAD3 genomes
AF:
0.0000263
AC:
4
AN:
151994
Hom.:
0
Cov.:
28
show subpopulations
Gnomad AFR
AF:
0.0000242
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:
0.0000441
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000835
AC:
21
AN:
251484
Hom.:
0
AF XY:
0.0000809
AC XY:
11
AN XY:
135914
show subpopulations
Gnomad AFR exome
AF:
0.0000615
Gnomad AMR exome
AF:
0.0000867
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000294
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000703
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000410
AC:
60
AN:
1461880
Hom.:
0
Cov.:
32
AF XY:
0.0000495
AC XY:
36
AN XY:
727246
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.0000671
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000406
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000180
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000263
AC:
4
AN:
151994
Hom.:
0
Cov.:
28
AF XY:
0.0000135
AC XY:
1
AN XY:
74246
show subpopulations
Gnomad4 AFR
AF:
0.0000242
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:
0.0000441
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000546
Hom.:
0
Bravo
AF:
0.0000453
ExAC
AF:
0.000107
AC:
13
EpiCase
AF:
0.0000545
EpiControl
AF:
0.000178

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 GeneticsJun 17, 2024The c.253G>A (p.A85T) alteration is located in exon 4 (coding exon 3) of the CLEC10A gene. This alteration results from a G to A substitution at nucleotide position 253, causing the alanine (A) at amino acid position 85 to be replaced by a threonine (T). 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
0.083
BayesDel_addAF
Benign
-0.43
T
BayesDel_noAF
Benign
-0.55
CADD
Benign
4.7
DANN
Uncertain
1.0
DEOGEN2
Benign
0.015
T;.;.;.
Eigen
Benign
-0.22
Eigen_PC
Benign
-0.37
FATHMM_MKL
Benign
0.032
N
LIST_S2
Benign
0.47
T;T;T;T
M_CAP
Benign
0.011
T
MetaRNN
Benign
0.11
T;T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.8
L;.;L;L
MutationTaster
Benign
1.0
N;N;N;N
PrimateAI
Benign
0.31
T
PROVEAN
Benign
-1.4
N;N;.;.
REVEL
Benign
0.074
Sift
Benign
0.66
T;T;.;.
Sift4G
Benign
0.33
T;T;T;T
Polyphen
0.99
D;.;D;P
Vest4
0.066
MVP
0.46
MPC
0.33
ClinPred
0.13
T
GERP RS
1.5
Varity_R
0.031
gMVP
0.13

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: rs199755396; hg19: chr17-6980238; API