rs1190657861

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_005385.4(NKTR):c.8C>A(p.Ala3Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000014 in 1,424,360 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A3V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

NKTR
NM_005385.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.89

Publications

0 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:

SEC22C (HGNC:16828): (SEC22 homolog C, vesicle trafficking protein) This gene encodes a member of the SEC22 family of vesicle trafficking proteins. The encoded protein is localized to the endoplasmic reticulum and may play a role in the early stages of ER-Golgi protein trafficking. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Jan 2011]

SEC22C links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.16654229).

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	HGVSp	Effect	Exon Rank	Protein
NKTR	NM_005385.4	MANE Select	c.8C>A	p.Ala3Glu	missense	Exon 2 of 17	NP_005376.2
NKTR	NM_001349124.2		c.8C>A	p.Ala3Glu	missense	Exon 2 of 17	NP_001336053.1
NKTR	NM_001349125.2		c.-808C>A		5_prime_UTR	Exon 2 of 19	NP_001336054.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NKTR	ENST00000232978.13	TSL:1 MANE Select	c.8C>A	p.Ala3Glu	missense	Exon 2 of 17	ENSP00000232978.8	P30414
NKTR	ENST00000459950.1	TSL:1	n.92C>A		non_coding_transcript_exon	Exon 2 of 2
NKTR	ENST00000937553.1		c.8C>A	p.Ala3Glu	missense	Exon 2 of 17	ENSP00000607612.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000140

AC:

AN:

1424360

Hom.:

Cov.:

AF XY:

0.00000283

AC XY:

AN XY:

706440

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

31634

American (AMR)

AF:

0.00

AC:

AN:

39710

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25314

East Asian (EAS)

AF:

0.00

AC:

AN:

37024

South Asian (SAS)

AF:

0.00

AC:

AN:

80858

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50362

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4084

European-Non Finnish (NFE)

AF:

0.00000182

AC:

AN:

1096504

Other (OTH)

AF:

0.00

AC:

AN:

58870

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.250

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.58

BayesDel_addAF

Benign

-0.043

BayesDel_noAF

Benign

-0.30

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.055

Eigen

Benign

-0.093

Eigen_PC

Benign

0.010

FATHMM_MKL

Benign

0.42

LIST_S2

Benign

0.81

M_CAP

Benign

0.015

MetaRNN

Benign

0.17

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.87

PhyloP100

1.9

PrimateAI

Uncertain

0.76

PROVEAN

Benign

-1.3

REVEL

Benign

0.14

Sift

Uncertain

0.029

Sift4G

Benign

0.12

Polyphen

0.95

Vest4

0.48

MutPred

0.28

Gain of disorder (P = 0.0269)

MVP

0.29

MPC

1.2

ClinPred

0.89

GERP RS

5.2

PromoterAI

0.034

Neutral

(source)

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.0

Varity_R

0.45

gMVP

0.29

Mutation Taster

=76/24

polymorphism

(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