Genetic Variant NCR3:p.Ala182Gly (chr6-31589128-G-C) – 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_147130.3(NCR3):c.545C>G(p.Ala182Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 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. A182V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

NCR3
NM_147130.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.224

Publications

1 publications found

Variant links:

Genes affected

NCR3 (HGNC:19077): (natural cytotoxicity triggering receptor 3) The protein encoded by this gene is a natural cytotoxicity receptor (NCR) that may aid NK cells in the lysis of tumor cells. The encoded protein interacts with CD3-zeta (CD247), a T-cell receptor. A single nucleotide polymorphism in the 5' untranslated region of this gene has been associated with mild malaria suceptibility. Three transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, May 2010]

NCR3 links:

LST1 (HGNC:14189): (leukocyte specific transcript 1) The protein encoded by this gene is a membrane protein that can inhibit the proliferation of lymphocytes. Expression of this gene is enhanced by lipopolysaccharide, interferon-gamma, and bacteria. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2011]

LST1 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=0.038669735).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_147130.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NCR3	NM_147130.3	MANE Select	c.545C>G	p.Ala182Gly	missense	Exon 4 of 4	NP_667341.1	O14931-1
NCR3	NM_001145466.2		c.*66C>G		3_prime_UTR	Exon 4 of 4	NP_001138938.1	Q05D23
LST1	NM_205839.3	MANE Select	c.*452G>C		downstream_gene	N/A	NP_995311.2	O00453-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NCR3	ENST00000340027.10	TSL:1 MANE Select	c.545C>G	p.Ala182Gly	missense	Exon 4 of 4	ENSP00000342156.5	O14931-1
NCR3	ENST00000376073.8	TSL:1	c.*66C>G		3_prime_UTR	Exon 4 of 4	ENSP00000365241.4	O14931-3
NCR3	ENST00000934501.1		c.545C>G	p.Ala182Gly	missense	Exon 5 of 5	ENSP00000604560.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.061

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.77

CADD

Benign

0.68

(source)

DANN

Benign

0.44

DEOGEN2

Benign

0.0029

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.0066

M_CAP

Benign

0.0041

MetaRNN

Benign

0.039

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

PhyloP100

-0.22

PrimateAI

Benign

0.36

PROVEAN

Benign

-0.29

REVEL

Benign

0.015

Sift

Benign

0.66

Sift4G

Benign

0.52

Polyphen

0.049

Vest4

0.049

MutPred

0.13

Gain of sheet (P = 0.0827)

MVP

0.15

MPC

0.27

ClinPred

0.021

GERP RS

-2.4

Varity_R

0.018

gMVP

0.13

Mutation Taster

=99/1

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over