12-10415730-C-G

Variant summary

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

The NM_002261.3(KLRC3):ā€‹c.652G>Cā€‹(p.Asp218His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000124 in 1,613,752 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.0000066 ( 0 hom., cov: 32)
Exomes š‘“: 6.8e-7 ( 0 hom. )

Consequence

KLRC3
NM_002261.3 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0280
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]

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=0.11119518).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
KLRC3NM_002261.3 linkc.652G>C p.Asp218His missense_variant 6/7 ENST00000396439.7 NP_002252.2 Q07444-1
KLRC3NM_007333.2 linkc.652G>C p.Asp218His missense_variant 6/6 NP_031359.2 Q07444-2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
KLRC3ENST00000396439.7 linkc.652G>C p.Asp218His missense_variant 6/75 NM_002261.3 ENSP00000379716.3 Q07444-1
KLRC3ENST00000381903.2 linkc.652G>C p.Asp218His missense_variant 6/61 ENSP00000371328.2 Q07444-2
ENSG00000255641ENST00000539033.1 linkc.652G>C p.Asp218His missense_variant 6/71 ENSP00000437563.1 F5H6K3

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152178
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000192
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
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461456
Hom.:
0
Cov.:
30
AF XY:
0.00000138
AC XY:
1
AN XY:
727014
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152296
Hom.:
0
Cov.:
32
AF XY:
0.0000134
AC XY:
1
AN XY:
74460
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00

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 submitterclinical testingAmbry GeneticsMay 13, 2022The c.652G>C (p.D218H) alteration is located in exon 6 (coding exon 6) of the KLRC3 gene. This alteration results from a G to C substitution at nucleotide position 652, causing the aspartic acid (D) at amino acid position 218 to be replaced by a histidine (H). 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
-0.27
T
BayesDel_noAF
Benign
-0.62
CADD
Benign
2.1
DANN
Benign
0.41
DEOGEN2
Benign
0.029
T;.;.
Eigen
Benign
-1.3
Eigen_PC
Benign
-1.4
FATHMM_MKL
Benign
0.038
N
LIST_S2
Benign
0.068
T;T;T
M_CAP
Benign
0.0013
T
MetaRNN
Benign
0.11
T;T;T
MetaSVM
Benign
-0.99
T
MutationAssessor
Uncertain
2.0
M;M;.
PrimateAI
Benign
0.34
T
PROVEAN
Uncertain
-2.8
D;D;D
REVEL
Benign
0.032
Sift
Benign
0.047
D;D;D
Sift4G
Benign
0.13
T;T;T
Polyphen
0.0030
B;B;.
Vest4
0.22
MutPred
0.56
Gain of catalytic residue at L215 (P = 1e-04);Gain of catalytic residue at L215 (P = 1e-04);Gain of catalytic residue at L215 (P = 1e-04);
MVP
0.040
MPC
0.27, 0.069
ClinPred
0.39
T
GERP RS
-0.55
Varity_R
0.15
gMVP
0.25

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.

Other links and lift over

dbSNP: rs1591600250; hg19: chr12-10568329; API