Genetic Variant NM_001202439.3:c.269G>T (chr11-17356849-G-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_001202439.3(NCR3LG1):c.269G>T(p.Arg90Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000723 in 1,383,818 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R90Q) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 7.2e-7 ( 0 hom. )

Consequence

NCR3LG1
NM_001202439.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.27

Publications

0 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.36893553).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NCR3LG1	NM_001202439.3 link	c.269G>T	p.Arg90Leu	missense_variant	Exon 2 of 5	ENST00000338965.9	NP_001189368.1	Q68D85
NCR3LG1	XM_047426906.1 link	c.269G>T	p.Arg90Leu	missense_variant	Exon 2 of 6		XP_047282862.1
NCR3LG1	XM_011520074.4 link	c.182G>T	p.Arg61Leu	missense_variant	Exon 2 of 5		XP_011518376.1
NCR3LG1	XM_011520075.4 link	c.182G>T	p.Arg61Leu	missense_variant	Exon 2 of 5		XP_011518377.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NCR3LG1	ENST00000338965.9 link	c.269G>T	p.Arg90Leu	missense_variant	Exon 2 of 5	1	NM_001202439.3	ENSP00000341637.4		Q68D85
NCR3LG1	ENST00000530403.1 link	n.269G>T		non_coding_transcript_exon_variant	Exon 2 of 6	5		ENSP00000434394.1		Q68D85

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.23e-7

AC:

AN:

1383818

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

682844

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31594

American (AMR)

AF:

0.00

AC:

AN:

35700

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25182

East Asian (EAS)

AF:

0.00

AC:

AN:

35734

South Asian (SAS)

AF:

0.00

AC:

AN:

79228

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33896

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5690

European-Non Finnish (NFE)

AF:

9.27e-7

AC:

AN:

1078880

Other (OTH)

AF:

0.00

AC:

AN:

57914

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.48

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.43

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.13

Eigen

Benign

-0.19

Eigen_PC

Benign

-0.35

FATHMM_MKL

Benign

0.12

M_CAP

Benign

0.013

MetaRNN

Benign

0.37

MetaSVM

Benign

-0.96

MutationAssessor

Benign

1.8

PhyloP100

2.3

PrimateAI

Benign

0.28

PROVEAN

Pathogenic

-4.9

REVEL

Benign

0.078

Sift

Uncertain

0.017

Sift4G

Uncertain

0.012

Polyphen

1.0

Vest4

0.32

MutPred

0.46

Loss of methylation at R90 (P = 0.0885);

MVP

0.36

ClinPred

0.87

GERP RS

3.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Varity_R

0.40

gMVP

0.64

Mutation Taster

=78/22

polymorphism

(source)

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

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NM_001202439.3:c.269G>T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over