Variant 11-17352034-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001202439.3(NCR3LG1):c.65C>T(p.Thr22Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000364 in 1,345,278 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Uncertain significance (★).

Frequency

Genomes: not found (cov: 28)

Exomes 𝑓: 0.000036 ( 0 hom. )

Consequence

NCR3LG1
NM_001202439.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.680

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 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=0.0810118).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
NCR3LG1	NM_001202439.3 linkuse as main transcript	c.65C>T	p.Thr22Ile	missense_variant	1/5	ENST00000338965.9
NCR3LG1	XM_047426906.1 linkuse as main transcript	c.65C>T	p.Thr22Ile	missense_variant	1/6
NCR3LG1	XM_011520074.4 linkuse as main transcript	c.-667C>T		5_prime_UTR_variant	1/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NCR3LG1	ENST00000338965.9 linkuse as main transcript	c.65C>T	p.Thr22Ile	missense_variant	1/5	1	NM_001202439.3	P1
NCR3LG1	ENST00000530403.1 linkuse as main transcript	c.65C>T	p.Thr22Ile	missense_variant, NMD_transcript_variant	1/6	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.000145

AC:

AN:

103118

Hom.:

AF XY:

0.000224

AC XY:

AN XY:

57970

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:

0.000676

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000319

GnomAD4 exome

AF:

0.0000364

AC:

AN:

1345278

Hom.:

Cov.:

AF XY:

0.0000437

AC XY:

AN XY:

663162

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:

0.000632

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

ExAC

AF:

0.000120

AC:

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

Nov 08, 2022

The c.65C>T (p.T22I) alteration is located in exon 1 (coding exon 1) of the NCR3LG1 gene. This alteration results from a C to T substitution at nucleotide position 65, causing the threonine (T) at amino acid position 22 to be replaced by an isoleucine (I). 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

0.22

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.66

Cadd

Benign

Dann

Benign

0.92

DEOGEN2

Benign

0.0011

Eigen

Benign

-0.63

Eigen_PC

Benign

-0.86

FATHMM_MKL

Benign

0.052

M_CAP

Benign

0.015

MetaRNN

Benign

0.081

MetaSVM

Benign

-0.76

MutationAssessor

Benign

0.0

MutationTaster

Benign

1.0

PrimateAI

Benign

0.39

PROVEAN

Benign

0.050

REVEL

Benign

0.018

Sift

Uncertain

0.0060

Sift4G

Uncertain

0.046

Polyphen

0.98

Vest4

0.16

MutPred

0.40

Loss of disorder (P = 0.0515);

MVP

0.061

ClinPred

0.10

GERP RS

0.44

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.11

gMVP

0.27

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