3-42621436-C-G

Variant names:

• chr3-42621436-C-G
• NM_005385.4:c.294C>G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_005385.4(NKTR):​c.294C>G​(p.Asn98Lys) variant causes a missense change. The variant allele was found at a frequency of 0.000000688 in 1,453,604 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: 6.9e-7 (0 hom.)
• Consequence: NKTR NM_005385.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.72

Genes affected

NKTR (HGNC:7833): (natural killer cell triggering receptor) This gene encodes a membrane-anchored protein with a hydrophobic amino terminal domain and a cyclophilin-like PPIase domain. It is present on the surface of natural killer cells and facilitates their binding to targets. Its expression is regulated by IL2 activation of the cells. [provided by RefSeq, Jul 2008]

ZBTB47-AS1 (HGNC:41174): (ZBTB47 and NKTR antisense RNA 1)

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NKTR	NM_005385.4	c.294C>G	p.Asn98Lys	missense_variant	Exon 6 of 17	ENST00000232978.13	NP_005376.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NKTR	ENST00000232978.13	c.294C>G	p.Asn98Lys	missense_variant	Exon 6 of 17	1	NM_005385.4	ENSP00000232978.8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.88e-7 AC: 1 AN: 1453604 Hom.: 0 Cov.: 29 AF XY: 0.00000138 AC XY: 1 AN XY: 723320

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.02e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 07, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.294C>G (p.N98K) alteration is located in exon 6 (coding exon 5) of the NKTR gene. This alteration results from a C to G substitution at nucleotide position 294, causing the asparagine (N) at amino acid position 98 to be replaced by a lysine (K). 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	Pathogenic	0.99
BayesDel_addAF	Benign	-0.099	T
BayesDel_noAF	Benign	-0.38
CADD	Uncertain	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.089	T
Eigen	Pathogenic	0.74
Eigen_PC	Pathogenic	0.73
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.027	D
MetaRNN	Uncertain	0.69	D
MetaSVM	Benign	-0.54	T
MutationAssessor	Benign	1.9	L
PrimateAI	Pathogenic	0.85	D
PROVEAN	Uncertain	-3.4	D
REVEL	Uncertain	0.34
Sift	Uncertain	0.0070	D
Sift4G	Uncertain	0.010	D
Polyphen		1.0	D
Vest4		0.64
MutPred		0.71		Gain of methylation at N98 (P = 0.0011);
MVP		0.41
MPC		1.2
ClinPred		0.84	D
GERP RS		5.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.7
Varity_R		0.67
gMVP		0.82

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-42662928;