12-10420496-A-C

Variant names:

• chr12-10420496-A-C
• rs2682490
• NM_002261.3:c.55T>G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002261.3(KLRC3):​c.55T>G​(p.Trp19Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. W19P) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 21)
• Consequence: KLRC3 NM_002261.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.431

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]

ENSG00000255641 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.031159699).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KLRC3	NM_002261.3	c.55T>G	p.Trp19Gly	missense_variant	Exon 1 of 7	ENST00000396439.7	NP_002252.2
KLRC3	NM_007333.2	c.55T>G	p.Trp19Gly	missense_variant	Exon 1 of 6		NP_031359.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KLRC3	ENST00000396439.7	c.55T>G	p.Trp19Gly	missense_variant	Exon 1 of 7	5	NM_002261.3	ENSP00000379716.3
KLRC3	ENST00000381903.2	c.55T>G	p.Trp19Gly	missense_variant	Exon 1 of 6	1		ENSP00000371328.2
ENSG00000255641	ENST00000539033.1	c.332-1998T>G		intron_variant	Intron 3 of 6	1		ENSP00000437563.1

Frequencies

GnomAD3 genomes Cov.: 21

GnomAD4 exome Cov.: 40

GnomAD4 genome Cov.: 21

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.055
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	1.7
DANN	Benign	0.55
DEOGEN2	Benign	0.0033	T;.
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.0092	N
LIST_S2	Benign	0.13	T;T
M_CAP	Benign	0.00093	T
MetaRNN	Benign	0.031	T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.0	N;N
PrimateAI	Benign	0.31	T
PROVEAN	Benign	1.0	N;N
REVEL	Benign	0.057
Sift	Uncertain	0.0020	D;D
Sift4G	Uncertain	0.0030	D;D
Polyphen		0.0	B;B
Vest4		0.035
MutPred		0.30		Loss of MoRF binding (P = 0.0415);Loss of MoRF binding (P = 0.0415);
MVP		0.10
MPC		0.37
ClinPred		0.18	T
GERP RS		0.094
Varity_R		0.095
gMVP		0.064

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

Other links and lift over

dbSNP: rs2682490; hg19: chr12-10573095;