Variant 12-10052733-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_207345.4(CLEC9A):c.46G>A(p.Ala16Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00531 in 1,613,728 control chromosomes in the GnomAD database, including 403 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.028 ( 202 hom., cov: 32)

Exomes 𝑓: 0.0029 ( 201 hom. )

Consequence

CLEC9A
NM_207345.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -2.36

Variant links:

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]

CLEC9A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0014681816).

BP6

Variant 12-10052733-G-A is Benign according to our data. Variant chr12-10052733-G-A is described in ClinVar as [Benign]. Clinvar id is 768515.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0943 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CLEC9A	NM_207345.4 linkuse as main transcript	c.46G>A	p.Ala16Thr	missense_variant	4/9	ENST00000355819.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CLEC9A	ENST00000355819.6 linkuse as main transcript	c.46G>A	p.Ala16Thr	missense_variant	4/9	1	NM_207345.4	P1
CLEC9A	ENST00000544751.1 linkuse as main transcript	n.1193G>A		non_coding_transcript_exon_variant	3/3	1

Frequencies

GnomAD3 genomes

AF:

0.0282

AC:

4280

AN:

151972

Hom.:

200

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0969

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0138

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00962

Gnomad NFE

AF:

0.000265

Gnomad OTH

AF:

0.0197

GnomAD3 exomes

AF:

0.00730

AC:

1836

AN:

251434

Hom.:

AF XY:

0.00573

AC XY:

779

AN XY:

135894

show subpopulations

Gnomad AFR exome

AF:

0.0968

Gnomad AMR exome

AF:

0.00567

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000163

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000317

Gnomad OTH exome

AF:

0.00407

GnomAD4 exome

AF:

0.00293

AC:

4281

AN:

1461666

Hom.:

201

Cov.:

AF XY:

0.00246

AC XY:

1791

AN XY:

727136

show subpopulations

Gnomad4 AFR exome

AF:

0.0981

Gnomad4 AMR exome

AF:

0.00671

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000301

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000164

Gnomad4 OTH exome

AF:

0.00763

GnomAD4 genome

AF:

0.0282

AC:

4284

AN:

152062

Hom.:

202

Cov.:

AF XY:

0.0273

AC XY:

2030

AN XY:

74310

show subpopulations

Gnomad4 AFR

AF:

0.0968

Gnomad4 AMR

AF:

0.0137

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000265

Gnomad4 OTH

AF:

0.0195

Alfa

AF:

0.00488

Hom.:

Bravo

AF:

0.0321

ESP6500AA

AF:

0.0949

AC:

418

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00880

AC:

1068

Asia WGS

AF:

0.00404

AC:

AN:

3478

EpiCase

AF:

0.000164

EpiControl

AF:

0.000356

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 04, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.064

BayesDel_addAF

Benign

-0.84

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.0010

DANN

Benign

0.14

DEOGEN2

Benign

0.039

Eigen

Benign

-2.1

Eigen_PC

Benign

-2.1

FATHMM_MKL

Benign

0.0019

LIST_S2

Benign

0.47

MetaRNN

Benign

0.0015

MetaSVM

Benign

-0.92

MutationAssessor

Benign

-2.2

MutationTaster

Benign

1.0

PrimateAI

Benign

0.22

PROVEAN

Benign

1.1

REVEL

Benign

0.018

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.064

MVP

0.072

MPC

0.12

ClinPred

0.0099

GERP RS

-8.4

Varity_R

0.017

gMVP

0.054

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over