dbSNP rs372245669: NCR3:p.Thr29Ala (chr6-31590085-T-C) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_147130.3(NCR3):c.85A>G(p.Thr29Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000378 in 1,612,390 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000040 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000038 ( 0 hom. )

Consequence

NCR3
NM_147130.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.142

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.039642096).

BP6

Variant 6-31590085-T-C is Benign according to our data. Variant chr6-31590085-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 3403691.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NCR3	NM_147130.3 link	c.85A>G	p.Thr29Ala	missense_variant	Exon 2 of 4	ENST00000340027.10	NP_667341.1	O14931-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NCR3	ENST00000340027.10 link	c.85A>G	p.Thr29Ala	missense_variant	Exon 2 of 4	1	NM_147130.3	ENSP00000342156.5		O14931-1

Frequencies

GnomAD3 genomes

AF:

0.0000395

AC:

AN:

151846

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000484

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:

0.0000589

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000826

AC:

AN:

242160

Hom.:

AF XY:

0.00000755

AC XY:

AN XY:

132498

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:

0.0000187

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000377

AC:

AN:

1460544

Hom.:

Cov.:

AF XY:

0.0000330

AC XY:

AN XY:

726576

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:

0.0000486

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000395

AC:

AN:

151846

Hom.:

Cov.:

AF XY:

0.0000270

AC XY:

AN XY:

74118

show subpopulations

Gnomad4 AFR

AF:

0.0000484

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:

0.0000589

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000416

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000185

AC:

ExAC

AF:

0.00000849

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Sep 04, 2024

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.65

CADD

Benign

0.47

DANN

Benign

0.27

DEOGEN2

Benign

0.0040

T;.;.;.

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.0074

M_CAP

Benign

0.0091

MetaRNN

Benign

0.040

T;T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

-0.26

N;N;N;N

PrimateAI

Benign

0.37

PROVEAN

Benign

0.24

N;N;N;N

REVEL

Benign

0.022

Sift

Benign

0.73

T;T;T;T

Sift4G

Benign

0.12

T;T;T;T

Polyphen

0.021

B;.;B;.

Vest4

0.038

MVP

0.41

MPC

0.35

ClinPred

0.011

GERP RS

-1.3

Varity_R

0.22

gMVP

0.34

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