Genetic Variant NM_002975.3:c.961T>C (chr19-50725456-T-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_002975.3(CLEC11A):c.961T>C(p.Phe321Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000569 in 1,598,154 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 0.000072 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000055 ( 0 hom. )

Consequence

CLEC11A
NM_002975.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.02

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: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.058397382).

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.961T>C	p.Phe321Leu	missense	Exon 4 of 4	NP_002966.1	Q9Y240

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CLEC11A	ENST00000250340.9	TSL:1 MANE Select	c.961T>C	p.Phe321Leu	missense	Exon 4 of 4	ENSP00000250340.3	Q9Y240
CLEC11A	ENST00000599973.1	TSL:1	c.*56T>C		3_prime_UTR	Exon 4 of 4	ENSP00000471075.1	M0R081
CLEC11A	ENST00000883282.1		c.952T>C	p.Phe318Leu	missense	Exon 4 of 4	ENSP00000553341.1

Frequencies

GnomAD3 genomes

AF:

0.0000723

AC:

AN:

152092

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00317

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000107

AC:

AN:

234272

AF XY:

0.000101

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00221

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000382

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000553

AC:

AN:

1446062

Hom.:

Cov.:

AF XY:

0.0000586

AC XY:

AN XY:

716812

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32954

American (AMR)

AF:

0.00

AC:

AN:

43586

Ashkenazi Jewish (ASJ)

AF:

0.00245

AC:

AN:

25750

East Asian (EAS)

AF:

0.00

AC:

AN:

39222

South Asian (SAS)

AF:

0.00

AC:

AN:

85238

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51826

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5738

European-Non Finnish (NFE)

AF:

0.00000907

AC:

AN:

1102210

Other (OTH)

AF:

0.000118

AC:

AN:

59538

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

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:

0.0000723

AC:

AN:

152092

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74294

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41422

American (AMR)

AF:

0.00

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00317

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5174

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10610

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67992

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.516

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:

0.000272

Hom.:

Bravo

AF:

0.0000529

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000119

AC:

ExAC

AF:

0.0000667

AC:

ClinVar

ClinVar submissions

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

Pathogenic

0.99

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.41

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.14

Eigen

Benign

-0.28

Eigen_PC

Benign

-0.23

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.70

M_CAP

Benign

0.028

MetaRNN

Benign

0.058

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.0

PhyloP100

4.0

PrimateAI

Pathogenic

0.84

PROVEAN

Pathogenic

-5.2

REVEL

Benign

0.20

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.017

Polyphen

0.26

Vest4

0.41

MutPred

0.80

Loss of sheet (P = 0.0817)

MVP

0.42

MPC

1.0

ClinPred

0.47

GERP RS

3.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.73

gMVP

0.75

Mutation Taster

=71/29

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