17-7075152-A-G

Position:

• chr17-7075152-A-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001330070.2(CLEC10A):​c.772T>C​(p.Phe258Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 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)
• Consequence: CLEC10A NM_001330070.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.499

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06281486).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLEC10A	NM_001330070.2	c.772T>C	p.Phe258Leu	missense_variant	9/9	ENST00000416562.7	NP_001316999.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLEC10A	ENST00000416562.7	c.772T>C	p.Phe258Leu	missense_variant	9/9	5	NM_001330070.2	ENSP00000414938	A2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 19, 2022

The c.853T>C (p.F285L) alteration is located in exon 9 (coding exon 8) of the CLEC10A gene. This alteration results from a T to C substitution at nucleotide position 853, causing the phenylalanine (F) at amino acid position 285 to be replaced by a leucine (L). 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	0.80
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	15
DANN	Benign	0.93
DEOGEN2	Benign	0.0064	T;.;.
Eigen	Benign	-0.70
Eigen_PC	Benign	-0.56
FATHMM_MKL	Benign	0.46	N
LIST_S2	Benign	0.77	T;T;T
M_CAP	Benign	0.0051	T
MetaRNN	Benign	0.063	T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-0.96	N;.;.
MutationTaster	Benign	1.0	D;N;N;N
PrimateAI	Uncertain	0.48	T
PROVEAN	Benign	-1.9	N;.;.
REVEL	Benign	0.043
Sift	Benign	0.31	T;.;.
Sift4G	Benign	0.51	T;T;T
Polyphen		0.047	B;.;B
Vest4		0.20
MutPred		0.52		Gain of disorder (P = 0.1271);.;.;
MVP		0.12
MPC		0.28
ClinPred		0.18	T
GERP RS		2.6
Varity_R		0.23
gMVP		0.57

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-6978471;