6-31590057-G-A

Variant names:

• chr6-31590057-G-A
• NM_147130.3:c.113C>T

Variant summary

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

The NM_147130.3(NCR3):​c.113C>T​(p.Pro38Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,460,732 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: NCR3 NM_147130.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.45
• 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.113C>T	p.Pro38Leu	missense	Exon 2 of 4	NP_667341.1	O14931-1
	NCR3	NM_001145467.2		c.113C>T	p.Pro38Leu	missense	Exon 2 of 4	NP_001138939.1	O14931-2
	NCR3	NM_001145466.2		c.113C>T	p.Pro38Leu	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.113C>T	p.Pro38Leu	missense	Exon 2 of 4	ENSP00000342156.5	O14931-1
	NCR3	ENST00000376072.7	TSL:1	c.113C>T	p.Pro38Leu	missense	Exon 2 of 4	ENSP00000365240.3	O14931-2
	NCR3	ENST00000376073.8	TSL:1	c.113C>T	p.Pro38Leu	missense	Exon 2 of 4	ENSP00000365241.4	O14931-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460732 Hom.: 0 Cov.: 34 AF XY: 0.00000138 AC XY: 1 AN XY: 726680

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

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

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52274

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

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1112010

Other (OTH) AF: 0.00 AC: 0 AN: 60386

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	Benign	0.32
BayesDel_addAF	Uncertain	0.054	T
BayesDel_noAF	Benign	-0.16
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.16	T
Eigen	Uncertain	0.57
Eigen_PC	Uncertain	0.51
FATHMM_MKL	Uncertain	0.93	D
M_CAP	Benign	0.040	D
MetaRNN	Uncertain	0.72	D
MetaSVM	Benign	-0.39	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		4.4
PrimateAI	Benign	0.42	T
PROVEAN	Uncertain	-4.4	D
REVEL	Uncertain	0.39
Sift	Uncertain	0.0080	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.55
MutPred		0.69		Loss of glycosylation at P38 (P = 0.0596)
MVP		0.86
MPC		0.94
ClinPred		0.99	D
GERP RS		4.0
Varity_R		0.24
gMVP		0.58
Mutation Taster		=93/7	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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

hg19: chr6-31557834; COSMIC: COSV99278960; COSMIC: COSV99278960;