chr17-7078083-C-G

Variant names:

• chr17-7078083-C-G
• rs200835319
• NM_001330070.2:c.98G>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001330070.2(CLEC10A):​c.98G>C​(p.Arg33Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000316 in 1,613,534 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R33H) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.000026 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000032 (0 hom.)
• Consequence: CLEC10A NM_001330070.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.90

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]

ACMG classification

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=0.12545082).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLEC10A	NM_001330070.2	c.98G>C	p.Arg33Pro	missense_variant	Exon 3 of 9	ENST00000416562.7	NP_001316999.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLEC10A	ENST00000416562.7	c.98G>C	p.Arg33Pro	missense_variant	Exon 3 of 9	5	NM_001330070.2	ENSP00000414938.2
CLEC10A	ENST00000254868.8	c.98G>C	p.Arg33Pro	missense_variant	Exon 3 of 9	1		ENSP00000254868.4
CLEC10A	ENST00000571664.1	c.98G>C	p.Arg33Pro	missense_variant	Exon 3 of 9	1		ENSP00000460252.1
CLEC10A	ENST00000576617.5	c.98G>C	p.Arg33Pro	missense_variant	Exon 3 of 7	1		ENSP00000458728.1

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 AN: 152068 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

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: 0.00

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000171 AC: 43 AN: 251204 Hom.: 0 AF XY: 0.000133 AC XY: 18 AN XY: 135740

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00124

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000322 AC: 47 AN: 1461466 Hom.: 0 Cov.: 31 AF XY: 0.0000261 AC XY: 19 AN XY: 727070

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00103

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: 0.00

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 152068 Hom.: 0 Cov.: 31 AF XY: 0.0000404 AC XY: 3 AN XY: 74260

Gnomad4 AFR AF: 0.00

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: 0.00

Gnomad4 OTH AF: 0.00

Alfa AF: 0.0000210 Hom.: 0

Bravo AF: 0.0000869

ExAC AF: 0.000148 AC: 18

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 29, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.98G>C (p.R33P) alteration is located in exon 3 (coding exon 2) of the CLEC10A gene. This alteration results from a G to C substitution at nucleotide position 98, causing the arginine (R) at amino acid position 33 to be replaced by a proline (P). 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	0.14
BayesDel_addAF	Benign	-0.53	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	0.042
DANN	Benign	0.74
DEOGEN2	Benign	0.038	T;.;.;.
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.017	N
LIST_S2	Benign	0.21	T;T;T;T
M_CAP	Benign	0.0092	T
MetaRNN	Benign	0.13	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.9	L;.;L;L
PrimateAI	Benign	0.21	T
PROVEAN	Uncertain	-3.8	D;D;.;.
REVEL	Benign	0.11
Sift	Benign	0.033	D;D;.;.
Sift4G	Uncertain	0.039	D;D;D;D
Polyphen		0.0040	B;.;B;B
Vest4		0.13
MutPred		0.76		Loss of helix (P = 0.0093);Loss of helix (P = 0.0093);Loss of helix (P = 0.0093);Loss of helix (P = 0.0093);
MVP		0.17
MPC		0.39
ClinPred		0.071	T
GERP RS		-8.9
Varity_R		0.49
gMVP		0.22

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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

Other links and lift over

dbSNP: rs200835319; hg19: chr17-6981402;