12-8995272-C-A

Variant names:

• chr12-8995272-C-A
• NM_005810.4:c.341C>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_005810.4(KLRG1):​c.341C>A​(p.Thr114Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,455,006 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: KLRG1 NM_005810.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.06

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.067907035).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KLRG1	NM_005810.4	c.341C>A	p.Thr114Lys	missense_variant	Exon 3 of 5	ENST00000356986.8	NP_005801.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KLRG1	ENST00000356986.8	c.341C>A	p.Thr114Lys	missense_variant	Exon 3 of 5	1	NM_005810.4	ENSP00000349477.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1455006 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 723830

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.01e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.091
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	0.0010
DANN	Benign	0.29
DEOGEN2	Benign	0.21	.;.;T;.
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.0090	N
LIST_S2	Benign	0.12	T;T;T;T
M_CAP	Benign	0.0020	T
MetaRNN	Benign	0.068	T;T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.88	.;L;L;.
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-2.1	N;N;N;N
REVEL	Benign	0.060
Sift	Benign	0.35	T;T;T;T
Sift4G	Benign	0.89	T;T;T;T
Polyphen		0.017, 0.035	.;B;B;.
Vest4		0.13, 0.12
MutPred		0.51		.;Gain of catalytic residue at L111 (P = 0.0126);Gain of catalytic residue at L111 (P = 0.0126);.;
MVP		0.12
MPC		0.19
ClinPred		0.035	T
GERP RS		-0.46
Varity_R		0.11
gMVP		0.34

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: chr12-9147868;