Variant 11-17351974-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001202439.3(NCR3LG1):c.5C>A(p.Thr2Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000243 in 1,349,128 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000096 ( 0 hom., cov: 30)

Exomes 𝑓: 0.00026 ( 0 hom. )

Consequence

NCR3LG1
NM_001202439.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.166

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.04955855).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NCR3LG1	NM_001202439.3 link	c.5C>A	p.Thr2Lys	missense_variant	1/5	ENST00000338965.9	NP_001189368.1	Q68D85
NCR3LG1	XM_047426906.1 link	c.5C>A	p.Thr2Lys	missense_variant	1/6		XP_047282862.1
NCR3LG1	XM_011520074.4 link	c.-727C>A		upstream_gene_variant			XP_011518376.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NCR3LG1	ENST00000338965.9 link	c.5C>A	p.Thr2Lys	missense_variant	1/5	1	NM_001202439.3	ENSP00000341637.4		Q68D85
NCR3LG1	ENST00000530403.1 link	n.5C>A		non_coding_transcript_exon_variant	1/6	5		ENSP00000434394.1		Q68D85

Frequencies

GnomAD3 genomes

AF:

0.0000964

AC:

AN:

145282

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000500

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000182

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000704

AC:

AN:

127922

Hom.:

AF XY:

0.0000854

AC XY:

AN XY:

70218

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000140

Gnomad OTH exome

AF:

0.000522

GnomAD4 exome

AF:

0.000261

AC:

314

AN:

1203736

Hom.:

Cov.:

AF XY:

0.000235

AC XY:

139

AN XY:

591816

show subpopulations

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:

0.000321

Gnomad4 OTH exome

AF:

0.000109

GnomAD4 genome

AF:

0.0000963

AC:

AN:

145392

Hom.:

Cov.:

AF XY:

0.0000849

AC XY:

AN XY:

70708

show subpopulations

Gnomad4 AFR

AF:

0.0000499

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000182

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000434

Hom.:

Bravo

AF:

0.000102

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 24, 2023

The c.5C>A (p.T2K) alteration is located in exon 1 (coding exon 1) of the NCR3LG1 gene. This alteration results from a C to A substitution at nucleotide position 5, causing the threonine (T) at amino acid position 2 to be replaced by a lysine (K). 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

0.17

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.74

CADD

Benign

DANN

Benign

0.86

DEOGEN2

Benign

0.015

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.032

M_CAP

Benign

0.015

MetaRNN

Benign

0.050

MetaSVM

Benign

-0.92

MutationAssessor

Benign

0.0

PrimateAI

Uncertain

0.50

PROVEAN

Benign

0.85

REVEL

Benign

0.091

Sift

Uncertain

0.016

Sift4G

Benign

0.12

Polyphen

0.0010

Vest4

0.12

MutPred

0.28

Gain of MoRF binding (P = 0.0191);

MVP

0.030

ClinPred

0.022

GERP RS

0.44

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.078

gMVP

0.47

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