Variant chr12-9599835-G-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_002258.3(KLRB1):c.191C>G(p.Ser64Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000268 in 1,417,284 control chromosomes in the GnomAD database, including 1 homozygotes. 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: 33)

Exomes 𝑓: 0.000027 ( 1 hom. )

Consequence

KLRB1
NM_002258.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.450

Variant links:

Genes affected

KLRB1 (HGNC:6373): (killer cell lectin like receptor B1) Natural killer (NK) cells are lymphocytes that mediate cytotoxicity and secrete cytokines after immune stimulation. Several genes of the C-type lectin superfamily, including the rodent NKRP1 family of glycoproteins, are expressed by NK cells and may be involved in the regulation of NK cell function. The KLRB1 protein contains an extracellular domain with several motifs characteristic of C-type lectins, a transmembrane domain, and a cytoplasmic domain. The KLRB1 protein is classified as a type II membrane protein because it has an external C terminus. [provided by RefSeq, Jul 2008]

KLRB1 links:

ENSG00000284634 (HGNC:):

ENSG00000284634 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=0.15584898).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KLRB1	NM_002258.3 linkuse as main transcript	c.191C>G	p.Ser64Cys	missense_variant	3/6	ENST00000229402.4	NP_002249.1	Q12918

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
KLRB1	ENST00000229402.4 linkuse as main transcript	c.191C>G	p.Ser64Cys	missense_variant	3/6	1	NM_002258.3	ENSP00000229402.3	Q12918
ENSG00000284634	ENST00000641304.1 linkuse as main transcript	n.552-6518G>C		intron_variant
ENSG00000284634	ENST00000642112.1 linkuse as main transcript	n.2026-6518G>C		intron_variant

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000359

AC:

AN:

250976

Hom.:

AF XY:

0.0000590

AC XY:

AN XY:

135624

show subpopulations

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:

0.000261

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000268

AC:

AN:

1417284

Hom.:

Cov.:

AF XY:

0.0000381

AC XY:

AN XY:

707780

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:

0.000375

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.000102

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

ExAC

AF:

0.0000494

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

Aug 19, 2024

The c.191C>G (p.S64C) alteration is located in exon 3 (coding exon 3) of the KLRB1 gene. This alteration results from a C to G substitution at nucleotide position 191, causing the serine (S) at amino acid position 64 to be replaced by a cysteine (C). 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

0.079

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.60

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.0060

Eigen

Benign

-0.67

Eigen_PC

Benign

-0.83

FATHMM_MKL

Benign

0.0067

LIST_S2

Benign

0.48

M_CAP

Benign

0.0032

MetaRNN

Benign

0.16

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.1

PrimateAI

Benign

0.35

PROVEAN

Benign

-1.0

REVEL

Benign

0.14

Sift

Benign

0.16

Sift4G

Benign

0.11

Polyphen

0.97

Vest4

0.32

MutPred

0.51

Gain of sheet (P = 0.0073);

MVP

0.32

MPC

0.22

ClinPred

0.24

GERP RS

-0.31

Varity_R

0.047

gMVP

0.24

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

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