12-10420546-C-A

Variant names:

• chr12-10420546-C-A
• rs2682489
• NM_002261.3:c.5G>T
• KLRC3 p.Ser2Ile

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002261.3(KLRC3):​c.5G>T​(p.Ser2Ile) 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. 15/22 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. S2N) has been classified as Benign.

• Frequency: Genomes: not found (cov: 19)
• Consequence: KLRC3 NM_002261.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.196
• Publications: 15 publications found

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

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=0.13189626).

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.5G>T	p.Ser2Ile	missense	Exon 1 of 7	NP_002252.2	Q07444-1
	KLRC3	NM_007333.2		c.5G>T	p.Ser2Ile	missense	Exon 1 of 6	NP_031359.2	Q07444-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLRC3	ENST00000396439.7	TSL:5 MANE Select	c.5G>T	p.Ser2Ile	missense	Exon 1 of 7	ENSP00000379716.3	Q07444-1
	KLRC3	ENST00000381903.2	TSL:1	c.5G>T	p.Ser2Ile	missense	Exon 1 of 6	ENSP00000371328.2	Q07444-2
	ENSG00000255641	ENST00000539033.1	TSL:1	c.332-2048G>T		intron	N/A	ENSP00000437563.1	F5H6K3

Frequencies

GnomAD3 genomes Cov.: 19

GnomAD4 exome Cov.: 45

GnomAD4 genome Cov.: 19

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	9.7
DANN	Benign	0.94
DEOGEN2	Benign	0.055	T
Eigen	Benign	-0.95
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.022	N
LIST_S2	Benign	0.68	T
M_CAP	Benign	0.0022	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.7	L
PhyloP100		-0.20
PrimateAI	Benign	0.42	T
PROVEAN	Uncertain	-3.4	D
REVEL	Benign	0.023
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
PromoterAI		-0.018	Neutral
Varity_R		0.19
gMVP		0.10
Mutation Taster		=98/2	polymorphism

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2682489;

hg19: chr12-10573145;