Variant 6-31592893-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 1P and 3B. PP5BP4BS1_SupportingBS2_Supporting

The NM_147130.3(NCR3):c.-172G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0216 in 680,664 control chromosomes in the GnomAD database, including 294 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: 𝑓 0.023 ( 75 hom., cov: 31)

Exomes 𝑓: 0.021 ( 219 hom. )

Consequence

NCR3
NM_147130.3 5_prime_UTR

Scores

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: -2.02

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 -2 ACMG points.

PP5

Variant 6-31592893-C-T is Pathogenic according to our data. Variant chr6-31592893-C-T is described in ClinVar as [Pathogenic]. Clinvar id is 1803723.Status of the report is no_assertion_criteria_provided, 0 stars.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87). . Strength limited to SUPPORTING due to the PP5.

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.0233 (3539/152184) while in subpopulation AMR AF= 0.039 (595/15262). AF 95% confidence interval is 0.0364. There are 75 homozygotes in gnomad4. There are 1577 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

BS2

High Homozygotes in GnomAd4 at 75 AR geneVariant has number of homozygotes lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NCR3	NM_147130.3 linkuse as main transcript	c.-172G>A		5_prime_UTR_variant	1/4	ENST00000340027.10

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NCR3	ENST00000340027.10 linkuse as main transcript	c.-172G>A	5_prime_UTR_variant	1/4	1	NM_147130.3	P2	O14931-1
NCR3	ENST00000376072.7 linkuse as main transcript	c.-172G>A	5_prime_UTR_variant	1/4	1		A2	O14931-2
NCR3	ENST00000376073.8 linkuse as main transcript	c.-172G>A	5_prime_UTR_variant	1/4	1		A2	O14931-3
NCR3	ENST00000491161.1 linkuse as main transcript	n.67G>A	non_coding_transcript_exon_variant	1/4	5

Frequencies

GnomAD3 genomes

AF:

0.0233

AC:

3540

AN:

152066

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0244

Gnomad AMI

AF:

0.00330

Gnomad AMR

AF:

0.0390

Gnomad ASJ

AF:

0.0979

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00165

Gnomad FIN

AF:

0.00132

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.0217

Gnomad OTH

AF:

0.0398

GnomAD4 exome

AF:

0.0212

AC:

11182

AN:

528480

Hom.:

219

Cov.:

AF XY:

0.0200

AC XY:

5599

AN XY:

280500

show subpopulations

Gnomad4 AFR exome

AF:

0.0254

Gnomad4 AMR exome

AF:

0.0401

Gnomad4 ASJ exome

AF:

0.0935

Gnomad4 EAS exome

AF:

0.000126

Gnomad4 SAS exome

AF:

0.00194

Gnomad4 FIN exome

AF:

0.00191

Gnomad4 NFE exome

AF:

0.0219

Gnomad4 OTH exome

AF:

0.0292

GnomAD4 genome

AF:

0.0233

AC:

3539

AN:

152184

Hom.:

Cov.:

AF XY:

0.0212

AC XY:

1577

AN XY:

74390

show subpopulations

Gnomad4 AFR

AF:

0.0244

Gnomad4 AMR

AF:

0.0390

Gnomad4 ASJ

AF:

0.0979

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00166

Gnomad4 FIN

AF:

0.00132

Gnomad4 NFE

AF:

0.0217

Gnomad4 OTH

AF:

0.0393

Alfa

AF:

0.0237

Hom.:

Bravo

AF:

0.0273

Asia WGS

AF:

0.00202

AC:

AN:

3478

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Malaria, severe, susceptibility to

Pathogenic:1

Pathogenic, no assertion criteria provided

research

Center for Global Health, University of New Mexico Health Sciences Center, University of New Mexico

Dec 06, 2022

CC is wild type in the Luo (Kenya) population, TT is homozygous mutant. TT increases susceptibility to longitudinal (over 36 months) falciparum malaria episodes in children less than 48 months of age. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.71

DANN

Benign

0.76

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