rs769170305

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr12-10420493-G-T
• chr12-10420493-G-A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_002261.3(KLRC3):​c.58C>A​(p.Gln20Lys) 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. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 28)
  • Exomes 𝑓: 0.000016 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: KLRC3 NM_002261.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.38306057).

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>A	p.Gln20Lys	missense	Exon 1 of 7	NP_002252.2	Q07444-1
	KLRC3	NM_007333.2		c.58C>A	p.Gln20Lys	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.58C>A	p.Gln20Lys	missense	Exon 1 of 7	ENSP00000379716.3	Q07444-1
	KLRC3	ENST00000381903.2	TSL:1	c.58C>A	p.Gln20Lys	missense	Exon 1 of 6	ENSP00000371328.2	Q07444-2
	ENSG00000255641	ENST00000539033.1	TSL:1	c.332-1995C>A		intron	N/A	ENSP00000437563.1	F5H6K3

Frequencies

GnomAD3 genomes Cov.: 28

GnomAD2 exomes AF: 0.0000160 AC: 4 AN: 250048 AF XY: 0.0000222

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000109

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000164 AC: 24 AN: 1461172 Hom.: 0 Cov.: 46 AF XY: 0.0000234 AC XY: 17 AN XY: 726886

African (AFR) AF: 0.00 AC: 0 AN: 33452

American (AMR) AF: 0.00 AC: 0 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26114

East Asian (EAS) AF: 0.0000757 AC: 3 AN: 39648

South Asian (SAS) AF: 0.000186 AC: 16 AN: 86222

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53386

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111510

Other (OTH) AF: 0.0000497 AC: 3 AN: 60370

GnomAD4 genome Cov.: 28

ExAC AF: 0.0000247 AC: 3

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	3.7
DANN	Benign	0.88
DEOGEN2	Benign	0.062	T
Eigen	Benign	-0.80
Eigen_PC	Benign	-0.98
FATHMM_MKL	Benign	0.036	N
LIST_S2	Benign	0.70	T
M_CAP	Benign	0.0011	T
MetaRNN	Benign	0.38	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		0.26
PrimateAI	Benign	0.37	T
PROVEAN	Uncertain	-3.5	D
REVEL	Benign	0.031
Sift	Uncertain	0.021	D
Sift4G	Uncertain	0.010	D
Polyphen		0.12	B
Vest4		0.26
MutPred		0.39		Gain of methylation at Q20 (P = 0.0041)
MVP		0.25
MPC		0.36
ClinPred		0.39	T
GERP RS		0.68
PromoterAI		0.028	Neutral
Varity_R		0.24
gMVP		0.13
Mutation Taster		=98/2	polymorphism

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

Other links and lift over

dbSNP: rs769170305; hg19: chr12-10573092;