12-10416670-T-G

Variant names:

• chr12-10416670-T-G
• rs148120835
• NM_002261.3:c.584A>C

Variant summary

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

The NM_002261.3(KLRC3):​c.584A>C​(p.His195Pro) 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.

• Frequency: Genomes: not found (cov: 32)
• Consequence: KLRC3 NM_002261.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.916

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=0.08144289).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KLRC3	NM_002261.3	c.584A>C	p.His195Pro	missense_variant	Exon 5 of 7	ENST00000396439.7	NP_002252.2
KLRC3	NM_007333.2	c.584A>C	p.His195Pro	missense_variant	Exon 5 of 6		NP_031359.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KLRC3	ENST00000396439.7	c.584A>C	p.His195Pro	missense_variant	Exon 5 of 7	5	NM_002261.3	ENSP00000379716.3
KLRC3	ENST00000381903.2	c.584A>C	p.His195Pro	missense_variant	Exon 5 of 6	1		ENSP00000371328.2
ENSG00000255641	ENST00000539033.1	c.584A>C	p.His195Pro	missense_variant	Exon 5 of 7	1		ENSP00000437563.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000399 AC: 1 AN: 250676 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135478

Gnomad AFR exome AF: 0.0000616

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	1.6
DANN	Benign	0.45
DEOGEN2	Benign	0.017	T;.;.
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.0044	N
LIST_S2	Benign	0.70	T;T;T
M_CAP	Benign	0.0010	T
MetaRNN	Benign	0.081	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.67	N;N;.
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-1.4	N;N;N
REVEL	Benign	0.057
Sift	Benign	0.25	T;T;T
Sift4G	Benign	0.20	T;T;T
Polyphen		0.61	P;B;.
Vest4		0.085
MutPred		0.64		Gain of catalytic residue at A192 (P = 0.0035);Gain of catalytic residue at A192 (P = 0.0035);Gain of catalytic residue at A192 (P = 0.0035);
MVP		0.081
MPC		0.33, 0.083
ClinPred		0.051	T
GERP RS		-2.8
Varity_R		0.11
gMVP		0.36

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

Other links and lift over

dbSNP: rs148120835; hg19: chr12-10569269;