rs11575839

Positions:

• chr6-31590014-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_147130.3(NCR3):​c.156C>T​(p.Ser52Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0341 in 1,612,980 control chromosomes in the GnomAD database, including 2,111 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.048 (275 hom., cov: 32)
  • Exomes 𝑓: 0.033 (1836 hom.)
• Consequence: NCR3 NM_147130.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.98

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP7: Synonymous conserved (PhyloP=-1.98 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.151 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NCR3	NM_147130.3	c.156C>T	p.Ser52Ser	synonymous_variant	2/4	ENST00000340027.10	NP_667341.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NCR3	ENST00000340027.10	c.156C>T	p.Ser52Ser	synonymous_variant	2/4	1	NM_147130.3	ENSP00000342156.5

Frequencies

GnomAD3 genomes AF: 0.0478 AC: 7267 AN: 152090 Hom.: 274 Cov.: 32

Gnomad AFR AF: 0.0787

Gnomad AMI AF: 0.00879

Gnomad AMR AF: 0.0464

Gnomad ASJ AF: 0.0262

Gnomad EAS AF: 0.0385

Gnomad SAS AF: 0.161

Gnomad FIN AF: 0.0252

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0269

Gnomad OTH AF: 0.0531

GnomAD3 exomes AF: 0.0481 AC: 11823 AN: 245566 Hom.: 598 AF XY: 0.0540 AC XY: 7229 AN XY: 133912

Gnomad AFR exome AF: 0.0781

Gnomad AMR exome AF: 0.0254

Gnomad ASJ exome AF: 0.0296

Gnomad EAS exome AF: 0.0515

Gnomad SAS exome AF: 0.154

Gnomad FIN exome AF: 0.0271

Gnomad NFE exome AF: 0.0274

Gnomad OTH exome AF: 0.0432

GnomAD4 exome AF: 0.0327 AC: 47704 AN: 1460772 Hom.: 1836 Cov.: 34 AF XY: 0.0367 AC XY: 26699 AN XY: 726700

Gnomad4 AFR exome AF: 0.0791

Gnomad4 AMR exome AF: 0.0275

Gnomad4 ASJ exome AF: 0.0262

Gnomad4 EAS exome AF: 0.0346

Gnomad4 SAS exome AF: 0.155

Gnomad4 FIN exome AF: 0.0276

Gnomad4 NFE exome AF: 0.0217

Gnomad4 OTH exome AF: 0.0417

GnomAD4 genome AF: 0.0479 AC: 7291 AN: 152208 Hom.: 275 Cov.: 32 AF XY: 0.0502 AC XY: 3733 AN XY: 74402

Gnomad4 AFR AF: 0.0791

Gnomad4 AMR AF: 0.0463

Gnomad4 ASJ AF: 0.0262

Gnomad4 EAS AF: 0.0384

Gnomad4 SAS AF: 0.160

Gnomad4 FIN AF: 0.0252

Gnomad4 NFE AF: 0.0269

Gnomad4 OTH AF: 0.0539

Alfa AF: 0.0330 Hom.: 122

Bravo AF: 0.0475

Asia WGS AF: 0.115 AC: 397 AN: 3478

EpiCase AF: 0.0264

EpiControl AF: 0.0306

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.55
DANN	Benign	0.79

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

Other links and lift over

dbSNP: rs11575839; hg19: chr6-31557791; COSMIC: COSV53002771; COSMIC: COSV53002771;