6-31589818-C-G

Variant names:

• chr6-31589818-C-G
• rs756886201
• NM_147130.3:c.352G>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_147130.3(NCR3):​c.352G>C​(p.Gly118Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: NCR3 NM_147130.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.821
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.352G>C	p.Gly118Arg	missense	Exon 2 of 4	NP_667341.1	O14931-1
	NCR3	NM_001145467.2		c.352G>C	p.Gly118Arg	missense	Exon 2 of 4	NP_001138939.1	O14931-2
	NCR3	NM_001145466.2		c.352G>C	p.Gly118Arg	missense	Exon 2 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.352G>C	p.Gly118Arg	missense	Exon 2 of 4	ENSP00000342156.5	O14931-1
	NCR3	ENST00000376072.7	TSL:1	c.352G>C	p.Gly118Arg	missense	Exon 2 of 4	ENSP00000365240.3	O14931-2
	NCR3	ENST00000376073.8	TSL:1	c.352G>C	p.Gly118Arg	missense	Exon 2 of 4	ENSP00000365241.4	O14931-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.77
BayesDel_addAF	Uncertain	0.10	D
BayesDel_noAF	Benign	-0.090
CADD	Benign	17
DANN	Uncertain	1.0
DEOGEN2	Benign	0.059	T
Eigen	Benign	-0.25
Eigen_PC	Benign	-0.35
FATHMM_MKL	Benign	0.048	N
M_CAP	Benign	0.020	T
MetaRNN	Uncertain	0.56	D
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	L
PhyloP100		0.82
PrimateAI	Uncertain	0.53	T
PROVEAN	Uncertain	-3.1	D
REVEL	Uncertain	0.31
Sift	Benign	0.063	T
Sift4G	Benign	0.31	T
Polyphen		0.95	P
Vest4		0.51
MutPred		0.71		Gain of methylation at G118 (P = 0.0116)
MVP		0.79
MPC		0.91
ClinPred		0.98	D
GERP RS		3.1
Varity_R		0.46
gMVP		0.51
Mutation Taster		=83/17	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: rs756886201; hg19: chr6-31557595;