NM_147130.3:c.13C>T

Variant names:

• chr6-31592709-G-A
• rs111995403
• NM_147130.3:c.13C>T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6 BP7

The NM_147130.3(NCR3):​c.13C>T​(p.Leu5Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000294 in 1,612,878 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.00017 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00031 (0 hom.)
• Consequence: NCR3 NM_147130.3 synonymous
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 1.72
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP6: Variant 6-31592709-G-A is Benign according to our data. Variant chr6-31592709-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3044589.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=1.72 with no splicing effect.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NCR3	NM_147130.3	MANE Select	c.13C>T	p.Leu5Leu	synonymous	Exon 1 of 4	NP_667341.1	O14931-1
	NCR3	NM_001145467.2		c.13C>T	p.Leu5Leu	synonymous	Exon 1 of 4	NP_001138939.1	O14931-2
	NCR3	NM_001145466.2		c.13C>T	p.Leu5Leu	synonymous	Exon 1 of 4	NP_001138938.1	Q05D23

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NCR3	ENST00000340027.10	TSL:1 MANE Select	c.13C>T	p.Leu5Leu	synonymous	Exon 1 of 4	ENSP00000342156.5	O14931-1
	NCR3	ENST00000376072.7	TSL:1	c.13C>T	p.Leu5Leu	synonymous	Exon 1 of 4	ENSP00000365240.3	O14931-2
	NCR3	ENST00000376073.8	TSL:1	c.13C>T	p.Leu5Leu	synonymous	Exon 1 of 4	ENSP00000365241.4	O14931-3

Frequencies

GnomAD3 genomes AF: 0.000171 AC: 26 AN: 152176 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000241

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: 0.000367

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000146 AC: 36 AN: 246092 AF XY: 0.000127

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 FIN exome AF: 0.0000464

Gnomad NFE exome AF: 0.000318

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000307 AC: 448 AN: 1460702 Hom.: 0 Cov.: 31 AF XY: 0.000288 AC XY: 209 AN XY: 726652

African (AFR) AF: 0.0000299 AC: 1 AN: 33480

American (AMR) AF: 0.0000224 AC: 1 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.0000766 AC: 4 AN: 52246

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.000389 AC: 433 AN: 1112006

Other (OTH) AF: 0.000149 AC: 9 AN: 60386

GnomAD4 genome AF: 0.000171 AC: 26 AN: 152176 Hom.: 0 Cov.: 31 AF XY: 0.000175 AC XY: 13 AN XY: 74352

African (AFR) AF: 0.0000241 AC: 1 AN: 41428

American (AMR) AF: 0.00 AC: 0 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5204

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000367 AC: 25 AN: 68036

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.000331 Hom.: 0

Bravo AF: 0.000189

EpiCase AF: 0.000382

EpiControl AF: 0.000178

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	NCR3-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	11
DANN	Benign	0.87
PhyloP100		1.7
PromoterAI		-0.016	Neutral
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs111995403; hg19: chr6-31560486;