12-10061216-A-C

Position:

• chr12-10061216-A-C

Variant summary

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

The NM_207345.4(CLEC9A):​c.262A>C​(p.Ser88Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,874 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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: 6.8e-7 (0 hom.)
• Consequence: CLEC9A NM_207345.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.29

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=0.09705442).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CLEC9A	NM_207345.4	c.262A>C	p.Ser88Arg	missense_variant	6/9	ENST00000355819.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CLEC9A	ENST00000355819.6	c.262A>C	p.Ser88Arg	missense_variant	6/9	1	NM_207345.4	P1
CLEC9A	ENST00000538482.1	n.618A>C		non_coding_transcript_exon_variant	1/2	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459874 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 726254

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000166

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

Jan 26, 2022

The c.262A>C (p.S88R) alteration is located in exon 6 (coding exon 3) of the CLEC9A gene. This alteration results from a A to C substitution at nucleotide position 262, causing the serine (S) at amino acid position 88 to be replaced by an arginine (R). 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	0.13
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	13
DANN	Benign	0.92
DEOGEN2	Benign	0.051	T
Eigen	Benign	-0.86
Eigen_PC	Benign	-0.87
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.57	T
M_CAP	Benign	0.0045	T
MetaRNN	Benign	0.097	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	0.90	L
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.030	N
REVEL	Benign	0.037
Sift	Benign	0.18	T
Sift4G	Benign	0.10	T
Polyphen		0.0040	B
Vest4		0.35
MutPred		0.38		Gain of MoRF binding (P = 0.0227);
MVP		0.12
MPC		0.16
ClinPred		0.10	T
GERP RS		3.0
Varity_R		0.040
gMVP		0.12

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: chr12-10213815;