Genetic Variant NM_001202439.3:c.5C>G (chr11-17351974-C-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001202439.3(NCR3LG1):c.5C>G(p.Thr2Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000815 in 1,349,020 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 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. T2K) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000048 ( 0 hom., cov: 30)

Exomes 𝑓: 0.0000033 ( 0 hom. )

Consequence

NCR3LG1
NM_001202439.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.166

Publications

1 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:

LOC105376576 (HGNC:):

LOC105376576 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.04300204).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NCR3LG1	NM_001202439.3 link	c.5C>G	p.Thr2Arg	missense_variant	Exon 1 of 5	ENST00000338965.9	NP_001189368.1	Q68D85
NCR3LG1	XM_047426906.1 link	c.5C>G	p.Thr2Arg	missense_variant	Exon 1 of 6		XP_047282862.1
NCR3LG1	XM_011520074.4 link	c.-727C>G		upstream_gene_variant			XP_011518376.1
LOC105376576	XR_931094.3 link	n.-108G>C		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NCR3LG1	ENST00000338965.9 link	c.5C>G	p.Thr2Arg	missense_variant	Exon 1 of 5	1	NM_001202439.3	ENSP00000341637.4		Q68D85
NCR3LG1	ENST00000530403.1 link	n.5C>G		non_coding_transcript_exon_variant	Exon 1 of 6	5		ENSP00000434394.1		Q68D85

Frequencies

GnomAD3 genomes

AF:

0.0000482

AC:

AN:

145282

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000175

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000156

AC:

AN:

127922

AF XY:

0.0000142

show subpopulations

Gnomad AFR exome

AF:

0.000394

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000332

AC:

AN:

1203738

Hom.:

Cov.:

AF XY:

0.00000338

AC XY:

AN XY:

591818

show subpopulations

African (AFR)

AF:

0.000157

AC:

AN:

25470

American (AMR)

AF:

0.00

AC:

AN:

30110

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18284

East Asian (EAS)

AF:

0.00

AC:

AN:

18630

South Asian (SAS)

AF:

0.00

AC:

AN:

77480

European-Finnish (FIN)

AF:

0.00

AC:

AN:

18844

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4762

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

964116

Other (OTH)

AF:

0.00

AC:

AN:

46042

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000482

AC:

AN:

145282

Hom.:

Cov.:

AF XY:

0.0000283

AC XY:

AN XY:

70594

show subpopulations

African (AFR)

AF:

0.000175

AC:

AN:

39982

American (AMR)

AF:

0.00

AC:

AN:

14552

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3374

East Asian (EAS)

AF:

0.00

AC:

AN:

4464

South Asian (SAS)

AF:

0.00

AC:

AN:

4290

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9386

Middle Eastern (MID)

AF:

0.00

AC:

AN:

306

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

66034

Other (OTH)

AF:

0.00

AC:

AN:

2010

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000567

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.70

CADD

Benign

(source)

DANN

Benign

0.91

DEOGEN2

Benign

0.015

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.033

M_CAP

Benign

0.011

MetaRNN

Benign

0.043

MetaSVM

Benign

-0.91

MutationAssessor

Benign

0.0

PhyloP100

-0.17

PrimateAI

Uncertain

0.49

PROVEAN

Benign

0.36

REVEL

Benign

0.056

Sift

Uncertain

0.011

Sift4G

Benign

0.076

Polyphen

0.0060

Vest4

0.082

MutPred

0.32

Gain of methylation at T2 (P = 0.0117);

MVP

0.072

ClinPred

0.014

GERP RS

0.44

PromoterAI

-0.86

Under-expression

(source)

Varity_R

0.10

gMVP

0.47

Mutation Taster

=99/1

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.5C>G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over