Genetic Variant NM_002975.3:c.506G>A (chr19-50724581-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_002975.3(CLEC11A):c.506G>A(p.Arg169His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000769 in 1,429,630 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000047 ( 0 hom. )

Consequence

CLEC11A
NM_002975.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.787

Publications

0 publications found

Variant links:

Genes affected

CLEC11A (HGNC:10576): (C-type lectin domain containing 11A) This gene encodes a member of the C-type lectin superfamily. The encoded protein is a secreted sulfated glycoprotein and functions as a growth factor for primitive hematopoietic progenitor cells. An alternative splice variant has been described but its biological nature has not been determined. [provided by RefSeq, Jul 2008]

CLEC11A links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.16695589).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002975.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLEC11A	NM_002975.3	MANE Select	c.506G>A	p.Arg169His	missense	Exon 3 of 4	NP_002966.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
CLEC11A	ENST00000250340.9	TSL:1 MANE Select	c.506G>A	p.Arg169His	missense	Exon 3 of 4	ENSP00000250340.3
CLEC11A	ENST00000599973.1	TSL:1	c.506G>A	p.Arg169His	missense	Exon 3 of 4	ENSP00000471075.1
CLEC11A	ENST00000883282.1		c.497G>A	p.Arg166His	missense	Exon 3 of 4	ENSP00000553341.1

Frequencies

GnomAD3 genomes

AF:

0.0000328

AC:

AN:

152214

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

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

GnomAD2 exomes

AF:

0.00

AC:

AN:

49082

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000470

AC:

AN:

1277416

Hom.:

Cov.:

AF XY:

0.00000321

AC XY:

AN XY:

622240

show subpopulations

African (AFR)

AF:

0.0000394

AC:

AN:

25362

American (AMR)

AF:

0.00

AC:

AN:

20310

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19636

East Asian (EAS)

AF:

0.00

AC:

AN:

30732

South Asian (SAS)

AF:

0.0000157

AC:

AN:

63888

European-Finnish (FIN)

AF:

0.00

AC:

AN:

31316

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4170

European-Non Finnish (NFE)

AF:

0.00000389

AC:

AN:

1029004

Other (OTH)

AF:

0.00

AC:

AN:

52998

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000328

AC:

AN:

152214

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74376

show subpopulations

African (AFR)

AF:

0.0000965

AC:

AN:

41464

American (AMR)

AF:

0.00

AC:

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4836

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68022

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.445

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000227

ExAC

AF:

0.0000130

AC:

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.45

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.090

Eigen

Benign

-0.061

Eigen_PC

Benign

-0.017

FATHMM_MKL

Benign

0.43

LIST_S2

Benign

0.72

M_CAP

Uncertain

0.13

MetaRNN

Benign

0.17

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.8

PhyloP100

0.79

PrimateAI

Uncertain

0.77

PROVEAN

Benign

-1.7

REVEL

Benign

0.025

Sift

Benign

0.057

Sift4G

Uncertain

0.023

Polyphen

0.90

Vest4

0.16

MutPred

0.34

Loss of solvent accessibility (P = 0.0056)

MVP

0.86

MPC

0.83

ClinPred

0.91

GERP RS

2.4

Varity_R

0.046

gMVP

0.31

Mutation Taster

=84/16

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over