chr6-31589567-A-G

Position:

• chr6-31589567-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 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

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

Verdict is Uncertain_significance. Variant got 3 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NCR3	NM_147130.3	c.455T>C	p.Leu152Pro	missense_variant	3/4	ENST00000340027.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NCR3	ENST00000340027.10	c.455T>C	p.Leu152Pro	missense_variant	3/4	1	NM_147130.3	P2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 09, 2022

The c.455T>C (p.L152P) alteration is located in exon 3 (coding exon 3) of the NCR3 gene. This alteration results from a T to C substitution at nucleotide position 455, causing the leucine (L) at amino acid position 152 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

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;D;D;D
MetaSVM	Benign	-0.88	T
MutationAssessor	Benign	1.5	L;L;L;.
MutationTaster	Benign	0.87	N;N;N;N
PrimateAI	Benign	0.46	T
PROVEAN	Uncertain	-2.9	D;N;N;D
REVEL	Uncertain	0.36
Sift	Uncertain	0.0020	D;D;D;D
Sift4G	Uncertain	0.0030	D;D;D;D
Polyphen		1.0	D;.;D;.
Vest4		0.81
MutPred		0.63		Loss of stability (P = 0.0525);Loss of stability (P = 0.0525);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

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: rs1382217490; hg19: chr6-31557344;