chr12-8989642-G-C

Position:

• chr12-8989642-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005810.4(KLRG1):​c.7G>C​(p.Asp3His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: KLRG1 NM_005810.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.73

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]

ENSG00000257105 (HGNC:):

ACMG classification

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=0.20278537).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KLRG1	NM_005810.4	c.7G>C	p.Asp3His	missense_variant	1/5	ENST00000356986.8	NP_005801.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KLRG1	ENST00000356986.8	c.7G>C	p.Asp3His	missense_variant	1/5	1	NM_005810.4	ENSP00000349477.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 26

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 03, 2024

The c.7G>C (p.D3H) alteration is located in exon 1 (coding exon 1) of the KLRG1 gene. This alteration results from a G to C substitution at nucleotide position 7, causing the aspartic acid (D) at amino acid position 3 to be replaced by a histidine (H). 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	0.21
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.55	.;D
Eigen	Benign	-0.054
Eigen_PC	Benign	-0.20
FATHMM_MKL	Benign	0.090	N
LIST_S2	Benign	0.54	T;T
M_CAP	Benign	0.0016	T
MetaRNN	Benign	0.20	T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.6	L;L
PrimateAI	Benign	0.45	T
PROVEAN	Uncertain	-3.9	D;D
REVEL	Benign	0.050
Sift	Uncertain	0.0040	D;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		1.0	D;D
Vest4		0.22
MutPred		0.40		Gain of catalytic residue at V5 (P = 0);Gain of catalytic residue at V5 (P = 0);
MVP		0.37
MPC		0.69
ClinPred		0.95	D
GERP RS		3.0
Varity_R		0.19
gMVP		0.45

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-9142238;