NM_002261.3:c.335G>T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_002261.3(KLRC3):c.335G>T(p.Arg112Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00149 in 1,574,494 control chromosomes in the GnomAD database, including 28 homozygotes. 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 Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R112H) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0076 ( 13 hom., cov: 34)

Exomes 𝑓: 0.00083 ( 15 hom. )

Consequence

KLRC3
NM_002261.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -3.68

Publications

0 publications found

Variant links:

Genes affected

KLRC3 (HGNC:6376): (killer cell lectin like receptor C3) Natural killer (NK) cells are lymphocytes that can mediate lysis of certain tumor cells and virus-infected cells without previous activation. They can also regulate specific humoral and cell-mediated immunity. NK cells preferentially express several calcium-dependent (C-type) lectins, which have been implicated in the regulation of NK cell function. KLRC3 is a member of the NKG2 group which are expressed primarily in natural killer (NK) cells and encodes a family of transmembrane proteins characterized by a type II membrane orientation (extracellular C terminus) and the presence of a C-type lectin domain. The NKG2 gene family is located within the NK complex, a region that contains several C-type lectin genes preferentially expressed on NK cells. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

KLRC3 links:

ENSG00000255641 (HGNC:):

ENSG00000255641 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004924208).

BP6

Variant 12-10418495-C-A is Benign according to our data. Variant chr12-10418495-C-A is described in ClinVar as Benign. ClinVar VariationId is 786221.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00765 (1164/152236) while in subpopulation AFR AF = 0.0269 (1117/41546). AF 95% confidence interval is 0.0256. There are 13 homozygotes in GnomAd4. There are 534 alleles in the male GnomAd4 subpopulation. Median coverage is 34. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 13 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002261.3. 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
	KLRC3	NM_002261.3	MANE Select	c.335G>T	p.Arg112Leu	missense	Exon 4 of 7	NP_002252.2	Q07444-1
	KLRC3	NM_007333.2		c.335G>T	p.Arg112Leu	missense	Exon 4 of 6	NP_031359.2	Q07444-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
KLRC3	ENST00000396439.7	TSL:5 MANE Select	c.335G>T	p.Arg112Leu	missense	Exon 4 of 7	ENSP00000379716.3	Q07444-1
KLRC3	ENST00000381903.2	TSL:1	c.335G>T	p.Arg112Leu	missense	Exon 4 of 6	ENSP00000371328.2	Q07444-2
ENSG00000255641	ENST00000539033.1	TSL:1	c.335G>T	p.Arg112Leu	missense	Exon 4 of 7	ENSP00000437563.1	F5H6K3

Frequencies

GnomAD3 genomes

AF:

0.00763

AC:

1160

AN:

152118

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0269

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00216

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:

0.0000588

Gnomad OTH

AF:

0.00478

GnomAD2 exomes

AF:

0.00219

AC:

517

AN:

235728

AF XY:

0.00161

show subpopulations

Gnomad AFR exome

AF:

0.0291

Gnomad AMR exome

AF:

0.00131

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000641

Gnomad OTH exome

AF:

0.00141

GnomAD4 exome

AF:

0.000828

AC:

1177

AN:

1422258

Hom.:

Cov.:

AF XY:

0.000709

AC XY:

503

AN XY:

709046

show subpopulations

African (AFR)

AF:

0.0295

AC:

950

AN:

32208

American (AMR)

AF:

0.00146

AC:

AN:

42348

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25426

East Asian (EAS)

AF:

0.00

AC:

AN:

39406

South Asian (SAS)

AF:

0.0000480

AC:

AN:

83388

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53240

Middle Eastern (MID)

AF:

0.00194

AC:

AN:

5660

European-Non Finnish (NFE)

AF:

0.0000388

AC:

AN:

1081568

Other (OTH)

AF:

0.00183

AC:

108

AN:

59014

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

100

149

199

249

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

128

160

<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:

0.00765

AC:

1164

AN:

152236

Hom.:

Cov.:

AF XY:

0.00717

AC XY:

534

AN XY:

74432

show subpopulations

African (AFR)

AF:

0.0269

AC:

1117

AN:

41546

American (AMR)

AF:

0.00216

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.00

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10600

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000588

AC:

AN:

68020

Other (OTH)

AF:

0.00473

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

130

195

260

325

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00358

Hom.:

Bravo

AF:

0.00879

ESP6500AA

AF:

0.0241

AC:

106

ESP6500EA

AF:

0.000117

AC:

ExAC

AF:

0.00267

AC:

324

EpiCase

AF:

0.0000546

EpiControl

AF:

0.0000593

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.095

BayesDel_addAF

Benign

-0.72

BayesDel_noAF

Benign

-0.79

CADD

Benign

0.0050

(source)

DANN

Benign

0.19

DEOGEN2

Benign

0.0044

Eigen

Benign

-2.2

Eigen_PC

Benign

-2.3

FATHMM_MKL

Benign

0.0016

LIST_S2

Benign

0.15

MetaRNN

Benign

0.0049

MetaSVM

Benign

-0.90

MutationAssessor

Benign

1.3

PhyloP100

-3.7

PrimateAI

Benign

0.27

PROVEAN

Benign

-0.12

REVEL

Benign

0.030

Sift

Benign

0.60

Sift4G

Benign

0.54

Polyphen

0.0090

Vest4

0.12

MVP

0.16

MPC

0.27

ClinPred

0.00084

GERP RS

-4.8

Varity_R

0.042

gMVP

0.22

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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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