Variant 12-10018444-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001129998.3(CLEC12B):c.794A>T(p.Lys265Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000877 in 1,551,002 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00039 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000055 ( 0 hom. )

Consequence

CLEC12B
NM_001129998.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.37

Variant links:

Genes affected

CLEC12B (HGNC:31966): (C-type lectin domain family 12 member B) Enables protein phosphatase binding activity and signaling receptor inhibitor activity. Involved in natural killer cell inhibitory signaling pathway; negative regulation of natural killer cell mediated cytotoxicity; and negative regulation of signaling receptor activity. Located in external side of plasma membrane. Part of protein-containing complex. [provided by Alliance of Genome Resources, Apr 2022]

CLEC12B links:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.12802628).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLEC12B	NM_001129998.3 linkuse as main transcript	c.794A>T	p.Lys265Met	missense_variant	6/6	ENST00000338896.11	NP_001123470.1
LOC102724020	NR_169587.1 linkuse as main transcript	n.258-2296T>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLEC12B	ENST00000338896.11 linkuse as main transcript	c.794A>T	p.Lys265Met	missense_variant	6/6	1	NM_001129998.3	ENSP00000344563	P1	Q2HXU8-1
CLEC12B	ENST00000544853.5 linkuse as main transcript	c.*242A>T		3_prime_UTR_variant, NMD_transcript_variant	6/6	1		ENSP00000439561		Q2HXU8-2
	ENST00000544225.1 linkuse as main transcript	n.249-2671T>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.000388

AC:

AN:

152222

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00140

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000134

AC:

AN:

156402

Hom.:

AF XY:

0.000121

AC XY:

AN XY:

82834

show subpopulations

Gnomad AFR exome

AF:

0.00226

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000165

Gnomad OTH exome

AF:

0.000455

GnomAD4 exome

AF:

0.0000551

AC:

AN:

1398662

Hom.:

Cov.:

AF XY:

0.0000594

AC XY:

AN XY:

689814

show subpopulations

Gnomad4 AFR exome

AF:

0.00143

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:

0.0000185

Gnomad4 OTH exome

AF:

0.000207

GnomAD4 genome

AF:

0.000387

AC:

AN:

152340

Hom.:

Cov.:

AF XY:

0.000255

AC XY:

AN XY:

74494

show subpopulations

Gnomad4 AFR

AF:

0.00139

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000214

Hom.:

Bravo

AF:

0.000442

ExAC

AF:

0.0000805

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 01, 2021

The c.794A>T (p.K265M) alteration is located in exon 6 (coding exon 6) of the CLEC12B gene. This alteration results from a A to T substitution at nucleotide position 794, causing the lysine (K) at amino acid position 265 to be replaced by a methionine (M). 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

0.24

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.23

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.068

Eigen

Uncertain

0.43

Eigen_PC

Uncertain

0.29

FATHMM_MKL

Uncertain

0.80

LIST_S2

Benign

0.54

M_CAP

Benign

0.0085

MetaRNN

Benign

0.13

MetaSVM

Benign

-0.79

MutationAssessor

Uncertain

2.6

MutationTaster

Benign

0.80

PrimateAI

Uncertain

0.55

PROVEAN

Uncertain

-3.8

REVEL

Benign

0.26

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.0020

Polyphen

1.0

Vest4

0.55

MVP

0.58

MPC

0.49

ClinPred

0.17

GERP RS

3.7

Varity_R

0.59

gMVP

0.55

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

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