NM_147130.3:c.455T>C

Variant names:

• chr6-31589567-A-G
• rs1382217490
• NM_147130.3:c.455T>C

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_147130.3(NCR3):​c.455T>C​(p.Leu152Pro) 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 pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: NCR3 NM_147130.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.47
• 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: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.827

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.455T>C	p.Leu152Pro	missense	Exon 3 of 4	NP_667341.1	O14931-1
	NCR3	NM_001145467.2		c.455T>C	p.Leu152Pro	missense	Exon 3 of 4	NP_001138939.1	O14931-2
	NCR3	NM_001145466.2		c.455T>C	p.Leu152Pro	missense	Exon 3 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.455T>C	p.Leu152Pro	missense	Exon 3 of 4	ENSP00000342156.5	O14931-1
	NCR3	ENST00000376072.7	TSL:1	c.455T>C	p.Leu152Pro	missense	Exon 3 of 4	ENSP00000365240.3	O14931-2
	NCR3	ENST00000376073.8	TSL:1	c.455T>C	p.Leu152Pro	missense	Exon 3 of 4	ENSP00000365241.4	O14931-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00 AC: 0 AN: 248398 AF XY: 0.00

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: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.44
BayesDel_addAF	Pathogenic	0.26	D
BayesDel_noAF	Uncertain	0.13
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.021	T
Eigen	Uncertain	0.19
Eigen_PC	Benign	0.11
FATHMM_MKL	Benign	0.61	D
M_CAP	Benign	0.027	D
MetaRNN	Pathogenic	0.83	D
MetaSVM	Benign	-0.88	T
MutationAssessor	Benign	1.5	L
PhyloP100		2.5
PrimateAI	Benign	0.46	T
PROVEAN	Uncertain	-2.9	D
REVEL	Uncertain	0.36
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0030	D
Polyphen		1.0	D
Vest4		0.81
MutPred		0.63		Loss of stability (P = 0.0525)
MVP		0.80
MPC		1.1
ClinPred		0.95	D
GERP RS		3.0
Varity_R		0.32
gMVP		0.88
Mutation Taster		=87/13	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: rs1382217490; hg19: chr6-31557344;