11-17356869-C-A

Variant names:

• chr11-17356869-C-A
• NM_001202439.3:c.289C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001202439.3(NCR3LG1):​c.289C>A​(p.Pro97Thr) 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 benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: NCR3LG1 NM_001202439.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.313
• Publications: 0 publications found

Genes affected

NCR3LG1 (HGNC:42400): (natural killer cell cytotoxicity receptor 3 ligand 1) B7H6 belongs to the B7 family (see MIM 605402) and is selectively expressed on tumor cells. Interaction of B7H6 with NKp30 (NCR3; MIM 611550) results in natural killer (NK) cell activation and cytotoxicity (Brandt et al., 2009 [PubMed 19528259]).[supplied by OMIM, Jan 2011]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.051120043).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NCR3LG1	NM_001202439.3	c.289C>A	p.Pro97Thr	missense_variant	Exon 2 of 5	ENST00000338965.9	NP_001189368.1
NCR3LG1	XM_047426906.1	c.289C>A	p.Pro97Thr	missense_variant	Exon 2 of 6		XP_047282862.1
NCR3LG1	XM_011520074.4	c.202C>A	p.Pro68Thr	missense_variant	Exon 2 of 5		XP_011518376.1
NCR3LG1	XM_011520075.4	c.202C>A	p.Pro68Thr	missense_variant	Exon 2 of 5		XP_011518377.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NCR3LG1	ENST00000338965.9	c.289C>A	p.Pro97Thr	missense_variant	Exon 2 of 5	1	NM_001202439.3	ENSP00000341637.4
NCR3LG1	ENST00000530403.1	n.289C>A		non_coding_transcript_exon_variant	Exon 2 of 6	5		ENSP00000434394.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 03, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.289C>A (p.P97T) alteration is located in exon 2 (coding exon 2) of the NCR3LG1 gene. This alteration results from a C to A substitution at nucleotide position 289, causing the proline (P) at amino acid position 97 to be replaced by a threonine (T). 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	Benign	0.14
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	6.7
DANN	Benign	0.21
DEOGEN2	Benign	0.0017	T
Eigen	Benign	-0.93
Eigen_PC	Benign	-0.94
FATHMM_MKL	Benign	0.019	N
M_CAP	Benign	0.0082	T
MetaRNN	Benign	0.051	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	0.69	N
PhyloP100		0.31
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.10	N
REVEL	Benign	0.029
Sift	Benign	0.55	T
Sift4G	Benign	0.17	T
Polyphen		0.097	B
Vest4		0.077
MutPred		0.47		Gain of MoRF binding (P = 0.053);
MVP		0.048
ClinPred		0.057	T
GERP RS		2.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Varity_R		0.13
gMVP		0.35
Mutation Taster		=95/5	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr11-17378416;