NM_005385.4:c.526C>T

Variant names:

• chr3-42631292-C-T
• NM_005385.4:c.526C>T

Variant summary

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

The NM_005385.4(NKTR):​c.526C>T​(p.Leu176Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: NKTR NM_005385.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.17
• Publications: 0 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: 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_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.526C>T	p.Leu176Phe	missense	Exon 8 of 17	NP_005376.2
	NKTR	NM_001349124.2		c.526C>T	p.Leu176Phe	missense	Exon 8 of 17	NP_001336053.1
	NKTR	NM_001349125.2		c.-234C>T		5_prime_UTR	Exon 10 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.526C>T	p.Leu176Phe	missense	Exon 8 of 17	ENSP00000232978.8	P30414
	NKTR	ENST00000937553.1		c.526C>T	p.Leu176Phe	missense	Exon 8 of 17	ENSP00000607612.1
	NKTR	ENST00000970640.1		c.526C>T	p.Leu176Phe	missense	Exon 8 of 17	ENSP00000640699.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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	0.27
BayesDel_addAF	Benign	-0.027	T
BayesDel_noAF	Benign	-0.28
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.11	T
Eigen	Uncertain	0.30
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.069	D
MetaRNN	Uncertain	0.45	T
MetaSVM	Benign	-0.72	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		1.2
PrimateAI	Uncertain	0.67	T
PROVEAN	Uncertain	-3.7	D
REVEL	Benign	0.20
Sift	Uncertain	0.0010	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.93	P
Vest4		0.46
MutPred		0.66		Loss of catalytic residue at L176 (P = 0.026)
MVP		0.35
MPC		1.1
ClinPred		0.99	D
GERP RS		2.6
Varity_R		0.83
gMVP		0.66
Mutation Taster		=81/19	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

hg19: chr3-42672784;