rs2682489

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr12-10420546-C-T
• chr12-10420546-C-A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_002261.3(KLRC3):​c.5G>A​(p.Ser2Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.95 (58154 hom., cov: 19)
  • Exomes 𝑓: 0.71 (291638 hom.)
  • Failed GnomAD Quality Control
• Consequence: KLRC3 NM_002261.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=4.398491E-5).
• BP6: Variant 12-10420546-C-T is Benign according to our data. Variant chr12-10420546-C-T is described in ClinVar as Benign. ClinVar VariationId is 768517.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.953 is higher than 0.05.

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>A	p.Ser2Asn	missense	Exon 1 of 7	NP_002252.2	Q07444-1
	KLRC3	NM_007333.2		c.5G>A	p.Ser2Asn	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>A	p.Ser2Asn	missense	Exon 1 of 7	ENSP00000379716.3	Q07444-1
	KLRC3	ENST00000381903.2	TSL:1	c.5G>A	p.Ser2Asn	missense	Exon 1 of 6	ENSP00000371328.2	Q07444-2
	ENSG00000255641	ENST00000539033.1	TSL:1	c.332-2048G>A		intron	N/A	ENSP00000437563.1	F5H6K3

Frequencies

GnomAD3 genomes AF: 0.954 AC: 122030 AN: 127978 Hom.: 58095 Cov.: 19

Gnomad AFR AF: 0.936

Gnomad AMI AF: 0.975

Gnomad AMR AF: 0.967

Gnomad ASJ AF: 0.969

Gnomad EAS AF: 0.974

Gnomad SAS AF: 0.978

Gnomad FIN AF: 0.958

Gnomad MID AF: 0.990

Gnomad NFE AF: 0.956

Gnomad OTH AF: 0.950

GnomAD2 exomes AF: 0.662 AC: 131306 AN: 198474 AF XY: 0.654

Gnomad AFR exome AF: 0.797

Gnomad AMR exome AF: 0.710

Gnomad ASJ exome AF: 0.676

Gnomad EAS exome AF: 0.757

Gnomad FIN exome AF: 0.573

Gnomad NFE exome AF: 0.624

Gnomad OTH exome AF: 0.691

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR;InbreedingCoeff AF: 0.709 AC: 987155 AN: 1391388 Hom.: 291638 Cov.: 45 AF XY: 0.722 AC XY: 498093 AN XY: 689542

African (AFR) AF: 0.852 AC: 26296 AN: 30876

American (AMR) AF: 0.881 AC: 35132 AN: 39862

Ashkenazi Jewish (ASJ) AF: 0.886 AC: 20861 AN: 23554

East Asian (EAS) AF: 0.907 AC: 33784 AN: 37260

South Asian (SAS) AF: 0.873 AC: 69127 AN: 79174

European-Finnish (FIN) AF: 0.826 AC: 40622 AN: 49180

Middle Eastern (MID) AF: 0.779 AC: 4104 AN: 5270

European-Non Finnish (NFE) AF: 0.667 AC: 712891 AN: 1068898

Other (OTH) AF: 0.774 AC: 44338 AN: 57314

GnomAD4 genome AF: 0.954 AC: 122150 AN: 128100 Hom.: 58154 Cov.: 19 AF XY: 0.951 AC XY: 58455 AN XY: 61456

African (AFR) AF: 0.936 AC: 33979 AN: 36284

American (AMR) AF: 0.967 AC: 12138 AN: 12548

Ashkenazi Jewish (ASJ) AF: 0.969 AC: 2871 AN: 2962

East Asian (EAS) AF: 0.974 AC: 4324 AN: 4438

South Asian (SAS) AF: 0.978 AC: 3744 AN: 3830

European-Finnish (FIN) AF: 0.958 AC: 8038 AN: 8390

Middle Eastern (MID) AF: 0.989 AC: 277 AN: 280

European-Non Finnish (NFE) AF: 0.956 AC: 54433 AN: 56920

Other (OTH) AF: 0.950 AC: 1593 AN: 1676

Alfa AF: 0.892 Hom.: 9938

ExAC AF: 0.577 AC: 69850

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.050
BayesDel_addAF	Benign	-0.43	T
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.15
DANN	Benign	0.60
DEOGEN2	Benign	0.0030	T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.0033	N
LIST_S2	Benign	0.48	T
MetaRNN	Benign	0.000044	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.96	N
PhyloP100		-0.20
PrimateAI	Benign	0.42	T
PROVEAN	Benign	2.6	N
REVEL	Benign	0.012
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.031
MPC		0.20
ClinPred		0.0034	T
GERP RS		-1.0
PromoterAI		-0.018	Neutral
Varity_R		0.036
gMVP		0.024
Mutation Taster		=100/0	polymorphism (auto)

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: rs2682489; hg19: chr12-10573145; COSMIC: COSV67249828;