17-7078083-C-A

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001330070.2(CLEC10A):​c.98G>T​(p.Arg33Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000658 in 152,068 control chromosomes in the GnomAD database, with no homozygous occurrence. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R33P) has been classified as Uncertain significance.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 31)
• Consequence: CLEC10A NM_001330070.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.90
• Publications: 2 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001330070.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLEC10A	NM_001330070.2	MANE Select	c.98G>T	p.Arg33Leu	missense	Exon 3 of 9	NP_001316999.1	J3KR22
	CLEC10A	NM_182906.4		c.98G>T	p.Arg33Leu	missense	Exon 3 of 9	NP_878910.1	Q8IUN9-1
	CLEC10A	NM_006344.4		c.98G>T	p.Arg33Leu	missense	Exon 3 of 9	NP_006335.2	Q8IUN9-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLEC10A	ENST00000416562.7	TSL:5 MANE Select	c.98G>T	p.Arg33Leu	missense	Exon 3 of 9	ENSP00000414938.2	J3KR22
	CLEC10A	ENST00000254868.8	TSL:1	c.98G>T	p.Arg33Leu	missense	Exon 3 of 9	ENSP00000254868.4	Q8IUN9-1
	CLEC10A	ENST00000571664.1	TSL:1	c.98G>T	p.Arg33Leu	missense	Exon 3 of 9	ENSP00000460252.1	Q8IUN9-2

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 152068 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

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

GnomAD4 exome Cov.: 31

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 152068 Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1 AN XY: 74260

African (AFR) AF: 0.00 AC: 0 AN: 41396

American (AMR) AF: 0.00 AC: 0 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10600

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68022

Other (OTH) AF: 0.00 AC: 0 AN: 2090

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	0.34
DANN	Benign	0.97
DEOGEN2	Benign	0.047	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.015	N
LIST_S2	Benign	0.43	T
M_CAP	Benign	0.031	D
MetaRNN	Uncertain	0.57	D
MetaSVM	Benign	-0.71	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		-1.9
PrimateAI	Benign	0.21	T
PROVEAN	Uncertain	-4.4	D
REVEL	Benign	0.18
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.0070	D
Polyphen		0.36	B
Vest4		0.17
MutPred		0.75		Gain of loop (P = 0.0079)
MVP		0.22
MPC		0.79
ClinPred		0.94	D
GERP RS		-8.9
Varity_R		0.17
gMVP		0.16

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs200835319; hg19: chr17-6981402;