Genetic Variant KLRG1:p.Leu135Val (chr12-9009020-C-G) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_005810.4(KLRG1):c.403C>G(p.Leu135Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,690 control chromosomes in the GnomAD database, including 1 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L135M) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000014 ( 1 hom. )

Consequence

KLRG1
NM_005810.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0160

Publications

0 publications found

Variant links:

Genes affected

KLRG1 (HGNC:6380): (killer cell lectin like receptor G1) 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. The protein encoded by this gene belongs to the killer cell lectin-like receptor (KLR) family, which is a group of transmembrane proteins preferentially expressed in NK cells. Studies in mice suggested that the expression of this gene may be regulated by MHC class I molecules. [provided by RefSeq, Jun 2016]

KLRG1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005810.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
KLRG1	NM_005810.4	MANE Select	c.403C>G	p.Leu135Val	missense	Exon 4 of 5	NP_005801.3
KLRG1	NM_001329099.2		c.403C>G	p.Leu135Val	missense	Exon 4 of 6	NP_001316028.1	Q96E93-1
KLRG1	NM_001329101.2		c.166C>G	p.Leu56Val	missense	Exon 4 of 5	NP_001316030.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
KLRG1	ENST00000356986.8	TSL:1 MANE Select	c.403C>G	p.Leu135Val	missense	Exon 4 of 5	ENSP00000349477.3	Q96E93-2
KLRG1	ENST00000266551.8	TSL:1	c.403C>G	p.Leu135Val	missense	Exon 4 of 6	ENSP00000266551.4	Q96E93-1
KLRG1	ENST00000539240.5	TSL:3	c.166C>G	p.Leu56Val	missense	Exon 4 of 5	ENSP00000445627.1	F5H207

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461690

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727150

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44692

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26128

East Asian (EAS)

AF:

0.00

AC:

AN:

39680

South Asian (SAS)

AF:

0.0000232

AC:

AN:

86234

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53410

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111920

Other (OTH)

AF:

0.00

AC:

AN:

60380

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.37

BayesDel_addAF

Benign

-0.10

BayesDel_noAF

Benign

-0.38

CADD

Benign

(source)

DANN

Uncertain

0.97

DEOGEN2

Benign

0.39

Eigen

Benign

-0.20

Eigen_PC

Benign

-0.41

FATHMM_MKL

Benign

0.22

LIST_S2

Benign

0.75

M_CAP

Benign

0.0035

MetaRNN

Uncertain

0.49

MetaSVM

Benign

-0.97

MutationAssessor

Uncertain

2.6

PhyloP100

0.016

PrimateAI

Benign

0.38

PROVEAN

Uncertain

-3.0

REVEL

Benign

0.20

Sift

Uncertain

0.0050

Sift4G

Uncertain

0.0070

Polyphen

1.0

Vest4

0.52

MutPred

0.69

Gain of catalytic residue at W132 (P = 0)

MVP

0.36

MPC

0.56

ClinPred

0.88

GERP RS

-0.15

Varity_R

0.24

gMVP

0.54

Mutation Taster

=76/24

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over