17-7075432-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001330070.2(CLEC10A):​c.629C>T​(p.Thr210Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000726 in 1,376,750 control chromosomes in the GnomAD database, with no homozygous occurrence. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 7.3e-7 ( 0 hom. )

Consequence

CLEC10A
NM_001330070.2 missense

Scores

3
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.09
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CLEC10ANM_001330070.2 linkc.629C>T p.Thr210Ile missense_variant 8/9 ENST00000416562.7 NP_001316999.1 J3KR22

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CLEC10AENST00000416562.7 linkc.629C>T p.Thr210Ile missense_variant 8/95 NM_001330070.2 ENSP00000414938.2 J3KR22

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
7.26e-7
AC:
1
AN:
1376750
Hom.:
0
Cov.:
31
AF XY:
0.00000148
AC XY:
1
AN XY:
676320
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:
0.0000142
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.0000113

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 GeneticsMay 06, 2024The c.710C>T (p.T237I) alteration is located in exon 8 (coding exon 7) of the CLEC10A gene. This alteration results from a C to T substitution at nucleotide position 710, causing the threonine (T) at amino acid position 237 to be replaced by an isoleucine (I). 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
0.26
BayesDel_addAF
Benign
-0.23
T
BayesDel_noAF
Benign
-0.56
CADD
Benign
15
DANN
Uncertain
1.0
DEOGEN2
Benign
0.055
T;.;.
Eigen
Benign
-0.15
Eigen_PC
Benign
-0.26
FATHMM_MKL
Benign
0.34
N
LIST_S2
Benign
0.51
T;T;T
M_CAP
Benign
0.0067
T
MetaRNN
Uncertain
0.61
D;D;D
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.92
L;.;.
PrimateAI
Benign
0.38
T
PROVEAN
Uncertain
-3.9
D;.;.
REVEL
Benign
0.11
Sift
Benign
0.14
T;.;.
Sift4G
Benign
0.12
T;T;T
Polyphen
1.0
D;.;P
Vest4
0.49
MutPred
0.66
Gain of helix (P = 0.0854);.;.;
MVP
0.40
MPC
0.81
ClinPred
0.91
D
GERP RS
0.42
Varity_R
0.20
gMVP
0.59

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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: rs1358187733; hg19: chr17-6978751; API