NM_005385.4:c.1187G>T

Variant names:

• chr3-42636891-G-T
• rs147385453
• NM_005385.4:c.1187G>T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_005385.4(NKTR):​c.1187G>T​(p.Arg396Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000826 in 1,573,570 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R396Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: NKTR NM_005385.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.70
• Publications: 1 publications found

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

Our verdict: Likely_benign. The variant received -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.33540606).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005385.4. 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
	NKTR	NM_005385.4	MANE Select	c.1187G>T	p.Arg396Leu	missense	Exon 13 of 17	NP_005376.2
	NKTR	NM_001349124.2		c.1187G>T	p.Arg396Leu	missense	Exon 13 of 17	NP_001336053.1
	NKTR	NM_001349125.2		c.428G>T	p.Arg143Leu	missense	Exon 15 of 19	NP_001336054.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NKTR	ENST00000232978.13	TSL:1 MANE Select	c.1187G>T	p.Arg396Leu	missense	Exon 13 of 17	ENSP00000232978.8	P30414
	NKTR	ENST00000937553.1		c.1187G>T	p.Arg396Leu	missense	Exon 13 of 17	ENSP00000607612.1
	NKTR	ENST00000970640.1		c.1187G>T	p.Arg396Leu	missense	Exon 13 of 17	ENSP00000640699.1

Frequencies

GnomAD3 genomes AF: 0.0000657 AC: 10 AN: 152178 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000139 AC: 3 AN: 216210 AF XY: 0.00

Gnomad AFR exome AF: 0.000192

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000211 AC: 3 AN: 1421274 Hom.: 0 Cov.: 33 AF XY: 0.00000142 AC XY: 1 AN XY: 705584

African (AFR) AF: 0.0000648 AC: 2 AN: 30882

American (AMR) AF: 0.00 AC: 0 AN: 32590

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23746

East Asian (EAS) AF: 0.00 AC: 0 AN: 39506

South Asian (SAS) AF: 0.00 AC: 0 AN: 78772

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52330

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5536

European-Non Finnish (NFE) AF: 9.10e-7 AC: 1 AN: 1099432

Other (OTH) AF: 0.00 AC: 0 AN: 58480

GnomAD4 genome AF: 0.0000657 AC: 10 AN: 152296 Hom.: 0 Cov.: 32 AF XY: 0.0000672 AC XY: 5 AN XY: 74460

African (AFR) AF: 0.000241 AC: 10 AN: 41568

American (AMR) AF: 0.00 AC: 0 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68024

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.0000272 Hom.: 0

Bravo AF: 0.0000453

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00000824 AC: 1

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	Uncertain	0.52
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.23
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.26	T
Eigen	Pathogenic	0.72
Eigen_PC	Pathogenic	0.71
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.34	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		4.7
PrimateAI	Uncertain	0.68	T
PROVEAN	Uncertain	-3.5	D
REVEL	Benign	0.13
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.043	D
Polyphen		1.0	D
Vest4		0.64
MVP		0.25
MPC		0.18
ClinPred		0.88	D
GERP RS		5.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.57
gMVP		0.20
Mutation Taster		=65/35	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

dbSNP: rs147385453; hg19: chr3-42678383;