11-17367278-C-T

Position:

chr11-17367278-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The ENST00000338965.9(NCR3LG1):c.691C>T(p.Arg231Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00368 in 1,536,186 control chromosomes in the GnomAD database, including 19 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0024 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0038 ( 18 hom. )

Consequence

NCR3LG1
ENST00000338965.9 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.01

Variant links:

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]

NCR3LG1 links:

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]

KCNJ11 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.011164278).

BP6

Variant 11-17367278-C-T is Benign according to our data. Variant chr11-17367278-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3341562.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 18 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
NCR3LG1	NM_001202439.3 linkuse as main transcript	c.691C>T	p.Arg231Trp	missense_variant	3/5	ENST00000338965.9	NP_001189368.1
NCR3LG1	XM_047426906.1 linkuse as main transcript	c.691C>T	p.Arg231Trp	missense_variant	3/6		XP_047282862.1
NCR3LG1	XM_011520074.4 linkuse as main transcript	c.604C>T	p.Arg202Trp	missense_variant	3/5		XP_011518376.1
NCR3LG1	XM_011520075.4 linkuse as main transcript	c.604C>T	p.Arg202Trp	missense_variant	3/5		XP_011518377.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NCR3LG1	ENST00000338965.9 linkuse as main transcript	c.691C>T	p.Arg231Trp	missense_variant	3/5	1	NM_001202439.3	ENSP00000341637	P1
KCNJ11	ENST00000682764.1 linkuse as main transcript	c.*51-976G>A		intron_variant				ENSP00000506780		Q14654-2
NCR3LG1	ENST00000530403.1 linkuse as main transcript	c.691C>T	p.Arg231Trp	missense_variant, NMD_transcript_variant	3/6	5		ENSP00000434394

Frequencies

GnomAD3 genomes

AF:

0.00241

AC:

367

AN:

152164

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000941

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00288

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.000754

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00400

Gnomad OTH

AF:

0.000955

GnomAD3 exomes

AF:

0.00197

AC:

275

AN:

139620

Hom.:

AF XY:

0.00213

AC XY:

161

AN XY:

75606

show subpopulations

Gnomad AFR exome

AF:

0.000154

Gnomad AMR exome

AF:

0.00127

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000222

Gnomad FIN exome

AF:

0.00101

Gnomad NFE exome

AF:

0.00399

Gnomad OTH exome

AF:

0.00165

GnomAD4 exome

AF:

0.00382

AC:

5292

AN:

1383904

Hom.:

Cov.:

AF XY:

0.00367

AC XY:

2503

AN XY:

682896

show subpopulations

Gnomad4 AFR exome

AF:

0.000601

Gnomad4 AMR exome

AF:

0.000952

Gnomad4 ASJ exome

AF:

0.000357

Gnomad4 EAS exome

AF:

0.0000280

Gnomad4 SAS exome

AF:

0.000189

Gnomad4 FIN exome

AF:

0.00118

Gnomad4 NFE exome

AF:

0.00463

Gnomad4 OTH exome

AF:

0.00307

GnomAD4 genome

AF:

0.00241

AC:

367

AN:

152282

Hom.:

Cov.:

AF XY:

0.00211

AC XY:

157

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.000938

Gnomad4 AMR

AF:

0.00288

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.000754

Gnomad4 NFE

AF:

0.00400

Gnomad4 OTH

AF:

0.000945

Alfa

AF:

0.00294

Hom.:

Bravo

AF:

0.00229

TwinsUK

AF:

0.00620

AC:

ALSPAC

AF:

0.00623

AC:

ExAC

AF:

0.000742

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Aug 01, 2024

NCR3LG1: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.058

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.77

CADD

Benign

0.0020

DANN

Benign

0.66

DEOGEN2

Benign

0.0018

Eigen

Benign

-2.3

Eigen_PC

Benign

-2.4

FATHMM_MKL

Benign

0.0084

M_CAP

Benign

0.0017

MetaRNN

Benign

0.011

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.85

MutationTaster

Benign

1.0

PrimateAI

Benign

0.22

PROVEAN

Benign

-0.43

REVEL

Benign

0.072

Sift

Uncertain

0.025

Sift4G

Benign

0.11

Polyphen

0.011

Vest4

0.11

MVP

0.13

ClinPred

0.0044

GERP RS

-7.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.13

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over