12-10415678-G-T

Variant names:

• chr12-10415678-G-T
• rs200006578
• ENST00000381903.2:c.704C>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_007333.2(KLRC3):​c.704C>A​(p.Ala235Glu) 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. 13/18 in silico tools predict 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: 32)
• Consequence: KLRC3 NM_007333.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.34

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 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=0.07518101).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KLRC3	NM_002261.3	c.678+26C>A		intron_variant	Intron 6 of 6	ENST00000396439.7	NP_002252.2
KLRC3	NM_007333.2	c.704C>A	p.Ala235Glu	missense_variant	Exon 6 of 6		NP_031359.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KLRC3	ENST00000381903.2	c.704C>A	p.Ala235Glu	missense_variant	Exon 6 of 6	1		ENSP00000371328.2
KLRC3	ENST00000396439.7	c.678+26C>A		intron_variant	Intron 6 of 6	5	NM_002261.3	ENSP00000379716.3
ENSG00000255641	ENST00000539033.1	c.678+26C>A		intron_variant	Intron 6 of 6	1		ENSP00000437563.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.77
CADD	Benign	0.027
DANN	Benign	0.89
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.019	N
LIST_S2	Benign	0.21	T
M_CAP	Benign	0.0020	T
MetaRNN	Benign	0.075	T
MetaSVM	Benign	-0.92	T
PrimateAI	Benign	0.31	T
PROVEAN	Benign	0.32	N
REVEL	Benign	0.015
Sift	Pathogenic	0.0	D
Polyphen		0.11	B
Vest4		0.17
MutPred		0.52		Gain of catalytic residue at L238 (P = 0.0055);
MVP		0.048
MPC		0.85
ClinPred		0.33	T
GERP RS		-2.0
gMVP		0.096

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs200006578; hg19: chr12-10568277;