11-17367147-C-G

Position:

• chr11-17367147-C-G

Variant summary

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

The NM_001202439.3(NCR3LG1):​c.560C>G​(p.Pro187Arg) 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. 15/20 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)
• Consequence: NCR3LG1 NM_001202439.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.893

Genes affected

NCR3LG1 (HGNC:42400): (natural killer cell cytotoxicity receptor 3 ligand 1) B7H6 belongs to the B7 family (see MIM 605402) and is selectively expressed on tumor cells. Interaction of B7H6 with NKp30 (NCR3; MIM 611550) results in natural killer (NK) cell activation and cytotoxicity (Brandt et al., 2009 [PubMed 19528259]).[supplied by OMIM, Jan 2011]

KCNJ11 (HGNC:6257): (potassium inwardly rectifying channel subfamily J member 11) Potassium channels are present in most mammalian cells, where they participate in a wide range of physiologic responses. The protein encoded by this gene is an integral membrane protein and inward-rectifier type potassium channel. The encoded protein, which has a greater tendency to allow potassium to flow into a cell rather than out of a cell, is controlled by G-proteins and is found associated with the sulfonylurea receptor SUR. Mutations in this gene are a cause of familial persistent hyperinsulinemic hypoglycemia of infancy (PHHI), an autosomal recessive disorder characterized by unregulated insulin secretion. Defects in this gene may also contribute to autosomal dominant non-insulin-dependent diabetes mellitus type II (NIDDM), transient neonatal diabetes mellitus type 3 (TNDM3), and permanent neonatal diabetes mellitus (PNDM). Multiple alternatively spliced transcript variants that encode different protein isoforms have been described for this gene. [provided by RefSeq, Oct 2009]

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=0.059155434).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NCR3LG1	NM_001202439.3	c.560C>G	p.Pro187Arg	missense_variant	3/5	ENST00000338965.9	NP_001189368.1
NCR3LG1	XM_047426906.1	c.560C>G	p.Pro187Arg	missense_variant	3/6		XP_047282862.1
NCR3LG1	XM_011520074.4	c.473C>G	p.Pro158Arg	missense_variant	3/5		XP_011518376.1
NCR3LG1	XM_011520075.4	c.473C>G	p.Pro158Arg	missense_variant	3/5		XP_011518377.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NCR3LG1	ENST00000338965.9	c.560C>G	p.Pro187Arg	missense_variant	3/5	1	NM_001202439.3	ENSP00000341637.4
KCNJ11	ENST00000682764.1	c.*51-845G>C		intron_variant				ENSP00000506780.1
NCR3LG1	ENST00000530403.1	n.560C>G		non_coding_transcript_exon_variant	3/6	5		ENSP00000434394.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

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

Nov 26, 2024

The c.560C>G (p.P187R) alteration is located in exon 3 (coding exon 3) of the NCR3LG1 gene. This alteration results from a C to G substitution at nucleotide position 560, causing the proline (P) at amino acid position 187 to be replaced by an arginine (R). 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	0.077
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	0.11
DANN	Benign	0.68
DEOGEN2	Benign	0.00083	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.027	N
M_CAP	Benign	0.0041	T
MetaRNN	Benign	0.059	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.42	N
PrimateAI	Benign	0.28	T
PROVEAN	Benign	0.20	N
REVEL	Benign	0.012
Sift	Benign	0.10	T
Sift4G	Benign	0.35	T
Polyphen		0.33	B
Vest4		0.041
MutPred		0.47		Loss of methylation at K183 (P = 0.0666);
MVP		0.055
ClinPred		0.095	T
GERP RS		-6.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.11
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: chr11-17388694;