NM_005810.4:c.403C>A

Variant names:

• chr12-9009020-C-A
• rs768984841
• NM_005810.4:c.403C>A

Variant summary

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

The NM_005810.4(KLRG1):​c.403C>A​(p.Leu135Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: KLRG1 NM_005810.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0160
• Publications: 0 publications found

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]

ACMG classification

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLRG1	NM_005810.4	MANE Select	c.403C>A	p.Leu135Met	missense	Exon 4 of 5	NP_005801.3
	KLRG1	NM_001329099.2		c.403C>A	p.Leu135Met	missense	Exon 4 of 6	NP_001316028.1	Q96E93-1
	KLRG1	NM_001329101.2		c.166C>A	p.Leu56Met	missense	Exon 4 of 5	NP_001316030.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLRG1	ENST00000356986.8	TSL:1 MANE Select	c.403C>A	p.Leu135Met	missense	Exon 4 of 5	ENSP00000349477.3	Q96E93-2
	KLRG1	ENST00000266551.8	TSL:1	c.403C>A	p.Leu135Met	missense	Exon 4 of 6	ENSP00000266551.4	Q96E93-1
	KLRG1	ENST00000539240.5	TSL:3	c.166C>A	p.Leu56Met	missense	Exon 4 of 5	ENSP00000445627.1	F5H207

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

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	0.34
BayesDel_addAF	Benign	-0.089	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.44	T
Eigen	Benign	-0.019
Eigen_PC	Benign	-0.28
FATHMM_MKL	Benign	0.20	N
LIST_S2	Benign	0.65	T
M_CAP	Benign	0.0029	T
MetaRNN	Uncertain	0.52	D
MetaSVM	Benign	-0.86	T
MutationAssessor	Pathogenic	3.4	M
PhyloP100		0.016
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.19
Sift	Uncertain	0.0060	D
Sift4G	Uncertain	0.0080	D
Polyphen		1.0	D
Vest4		0.39
MutPred		0.68		Gain of catalytic residue at W132 (P = 0)
MVP		0.44
MPC		0.56
ClinPred		0.92	D
GERP RS		-0.15
Varity_R		0.34
gMVP		0.42
Mutation Taster		=77/23	polymorphism

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

Other links and lift over

dbSNP: rs768984841; hg19: chr12-9161616;