Variant 12-10418387-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000539033.1(ENSG00000255641):c.443A>C(p.Lys148Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000343 in 1,459,852 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

ENSG00000255641
ENST00000539033.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.401

Variant links:

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]

KLRC3 links:

ENSG00000255641 (HGNC:):

ENSG00000255641 links:

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ACMG classification

Classification made for transcript

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=0.23511562).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KLRC3	NM_002261.3 linkuse as main transcript	c.443A>C	p.Lys148Thr	missense_variant	4/7	ENST00000396439.7	NP_002252.2	Q07444-1
KLRC3	NM_007333.2 linkuse as main transcript	c.443A>C	p.Lys148Thr	missense_variant	4/6		NP_031359.2	Q07444-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
KLRC3	ENST00000396439.7 linkuse as main transcript	c.443A>C	p.Lys148Thr	missense_variant	4/7	5	NM_002261.3	ENSP00000379716.3	Q07444-1
KLRC3	ENST00000381903.2 linkuse as main transcript	c.443A>C	p.Lys148Thr	missense_variant	4/6	1		ENSP00000371328.2	Q07444-2
ENSG00000255641	ENST00000539033.1 linkuse as main transcript	c.443A>C	p.Lys148Thr	missense_variant	4/7	1		ENSP00000437563.1	F5H6K3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000159

AC:

AN:

251218

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135776

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000131

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000342

AC:

AN:

1459852

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

726344

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000580

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000247

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 05, 2023

The c.443A>C (p.K148T) alteration is located in exon 4 (coding exon 4) of the KLRC3 gene. This alteration results from a A to C substitution at nucleotide position 443, causing the lysine (K) at amino acid position 148 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.25

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.037

T;.;.

Eigen

Benign

-0.48

Eigen_PC

Benign

-0.82

FATHMM_MKL

Benign

0.044

LIST_S2

Benign

0.79

T;T;T

M_CAP

Benign

0.0011

MetaRNN

Benign

0.24

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.6

M;M;.

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Uncertain

0.56

PROVEAN

Uncertain

-4.2

D;D;D

REVEL

Benign

0.059

Sift

Uncertain

0.0010

D;D;D

Sift4G

Uncertain

0.0080

D;D;D

Polyphen

1.0

D;D;.

Vest4

0.38

MutPred

0.56

Gain of catalytic residue at S147 (P = 3e-04);Gain of catalytic residue at S147 (P = 3e-04);Gain of catalytic residue at S147 (P = 3e-04);

MVP

0.055

MPC

0.50, 0.36

ClinPred

0.59

GERP RS

-1.6

Varity_R

0.35

gMVP

0.32

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over