12-10054294-A-G

Position:

• chr12-10054294-A-G

Variant summary

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

The NM_207345.4(CLEC9A):​c.115A>G​(p.Ile39Val) 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: CLEC9A NM_207345.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.328

Genes affected

CLEC9A (HGNC:26705): (C-type lectin domain containing 9A) CLEC9A is a group V C-type lectin-like receptor (CTLR) that functions as an activation receptor and is expressed on myeloid lineage cells (Huysamen et al., 2008 [PubMed 18408006]).[supplied by OMIM, Aug 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=0.09376225).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CLEC9A	NM_207345.4	c.115A>G	p.Ile39Val	missense_variant	5/9	ENST00000355819.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CLEC9A	ENST00000355819.6	c.115A>G	p.Ile39Val	missense_variant	5/9	1	NM_207345.4	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

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

Apr 11, 2023

The c.115A>G (p.I39V) alteration is located in exon 5 (coding exon 2) of the CLEC9A gene. This alteration results from a A to G substitution at nucleotide position 115, causing the isoleucine (I) at amino acid position 39 to be replaced by a valine (V). 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	0.090
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	12
DANN	Uncertain	1.0
DEOGEN2	Benign	0.065	T
Eigen	Benign	-0.77
Eigen_PC	Benign	-0.73
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.50	T
M_CAP	Benign	0.0053	T
MetaRNN	Benign	0.094	T
MetaSVM	Benign	-0.89	T
MutationAssessor	Uncertain	2.3	M
MutationTaster	Benign	0.94	N
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-0.28	N
REVEL	Benign	0.033
Sift	Benign	0.13	T
Sift4G	Pathogenic	0.0	D
Polyphen		0.023	B
Vest4		0.065
MutPred		0.31		Gain of catalytic residue at V36 (P = 0);
MVP		0.23
MPC		0.12
ClinPred		0.11	T
GERP RS		0.22
Varity_R		0.043
gMVP		0.073

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: chr12-10206893;