12-10420493-G-A

Variant names:

• chr12-10420493-G-A
• rs769170305
• NM_002261.3:c.58C>T

Variant summary

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

The NM_002261.3(KLRC3):​c.58C>T​(p.Gln20*) variant causes a stop gained 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 28)
• Consequence: KLRC3 NM_002261.3 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.260
• Publications: 0 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.58C>T	p.Gln20*	stop_gained	Exon 1 of 7	NP_002252.2	Q07444-1
	KLRC3	NM_007333.2		c.58C>T	p.Gln20*	stop_gained	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.58C>T	p.Gln20*	stop_gained	Exon 1 of 7	ENSP00000379716.3	Q07444-1
	KLRC3	ENST00000381903.2	TSL:1	c.58C>T	p.Gln20*	stop_gained	Exon 1 of 6	ENSP00000371328.2	Q07444-2
	ENSG00000255641	ENST00000539033.1	TSL:1	c.332-1995C>T		intron	N/A	ENSP00000437563.1	F5H6K3

Frequencies

GnomAD3 genomes Cov.: 28

GnomAD4 exome Cov.: 46

GnomAD4 genome Cov.: 28

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.078	T
BayesDel_noAF	Benign	-0.35
CADD	Pathogenic	26
DANN	Uncertain	0.98
Eigen	Benign	-0.10
Eigen_PC	Benign	-0.52
FATHMM_MKL	Benign	0.029	N
PhyloP100		0.26
Vest4		0.71
GERP RS		0.68
PromoterAI		-0.0092	Neutral
Mutation Taster		=71/129	disease causing (fs/PTC)

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

Other links and lift over

dbSNP: rs769170305; hg19: chr12-10573092; COSMIC: COSV101122931;