Genetic Variant NKTR:c.59-5406G>A (chr3-42612164-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_005385.4(NKTR):c.59-5406G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.463 in 152,090 control chromosomes in the GnomAD database, including 18,913 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.46 ( 18913 hom., cov: 33)

Exomes 𝑓: 0.50 ( 0 hom. )

Consequence

NKTR
NM_005385.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.288

Publications

3 publications found

Variant links:

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]

NKTR links:

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

ZBTB47-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.04).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.735 is higher than 0.05.

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
NKTR	NM_005385.4	MANE Select	c.59-5406G>A	intron	N/A	NP_005376.2
NKTR	NM_001349124.2		c.59-5406G>A	intron	N/A	NP_001336053.1
NKTR	NM_001349125.2		c.-757-5406G>A	intron	N/A	NP_001336054.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
NKTR	ENST00000232978.13	TSL:1 MANE Select	c.59-5406G>A	intron	N/A	ENSP00000232978.8
NKTR	ENST00000442970.5	TSL:2	c.59-5406G>A	intron	N/A	ENSP00000390259.1
NKTR	ENST00000445842.1	TSL:5	c.59-5406G>A	intron	N/A	ENSP00000408660.1

Frequencies

GnomAD3 genomes

AF:

0.463

AC:

70337

AN:

151970

Hom.:

18869

Cov.:

show subpopulations

Gnomad AFR

AF:

0.741

Gnomad AMI

AF:

0.249

Gnomad AMR

AF:

0.321

Gnomad ASJ

AF:

0.310

Gnomad EAS

AF:

0.597

Gnomad SAS

AF:

0.500

Gnomad FIN

AF:

0.339

Gnomad MID

AF:

0.316

Gnomad NFE

AF:

0.344

Gnomad OTH

AF:

0.436

GnomAD4 exome

AF:

0.500

AC:

AN:

Hom.:

AF XY:

0.500

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.500

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.463

AC:

70439

AN:

152088

Hom.:

18913

Cov.:

AF XY:

0.464

AC XY:

34474

AN XY:

74334

show subpopulations

African (AFR)

AF:

0.742

AC:

30754

AN:

41460

American (AMR)

AF:

0.321

AC:

4911

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.310

AC:

1076

AN:

3472

East Asian (EAS)

AF:

0.597

AC:

3095

AN:

5184

South Asian (SAS)

AF:

0.500

AC:

2409

AN:

4818

European-Finnish (FIN)

AF:

0.339

AC:

3578

AN:

10566

Middle Eastern (MID)

AF:

0.313

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.344

AC:

23375

AN:

67986

Other (OTH)

AF:

0.437

AC:

922

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1732

3465

5197

6930

8662

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

626

1252

1878

2504

3130

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.421

Hom.:

5483

Bravo

AF:

0.470

Asia WGS

AF:

0.525

AC:

1828

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.56

(source)

DANN

Benign

0.22

PhyloP100

-0.29

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over