2-121730999-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_032390.5(NIFK):​c.458G>A​(p.Arg153Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000682 in 1,612,116 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 (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000068 ( 0 hom. )

Consequence

NIFK
NM_032390.5 missense

Scores

7
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.41
Variant links:
Genes affected
NIFK (HGNC:17838): (nucleolar protein interacting with the FHA domain of MKI67) This gene encodes a protein that interacts with the forkhead-associated domain of the Ki-67 antigen. The encoded protein may bind RNA and may play a role in mitosis and cell cycle progression. Multiple pseudogenes exist on chromosomes 5, 10, 12, 15, and 19.[provided by RefSeq, Jan 2009]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.27442622).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
NIFKNM_032390.5 linkc.458G>A p.Arg153Gln missense_variant 4/7 ENST00000285814.9 NP_115766.3 Q9BYG3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
NIFKENST00000285814.9 linkc.458G>A p.Arg153Gln missense_variant 4/71 NM_032390.5 ENSP00000285814.4 Q9BYG3

Frequencies

GnomAD3 genomes
AF:
0.00000658
AC:
1
AN:
152002
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000242
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
GnomAD3 exomes
AF:
0.0000159
AC:
4
AN:
251380
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135874
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000264
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000685
AC:
10
AN:
1460114
Hom.:
0
Cov.:
29
AF XY:
0.00000551
AC XY:
4
AN XY:
726524
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000232
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000630
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000658
AC:
1
AN:
152002
Hom.:
0
Cov.:
33
AF XY:
0.0000135
AC XY:
1
AN XY:
74210
show subpopulations
Gnomad4 AFR
AF:
0.0000242
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000329
Hom.:
0
Bravo
AF:
0.0000189
ExAC
AF:
0.00000824
AC:
1

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsJun 24, 2022The c.458G>A (p.R153Q) alteration is located in exon 4 (coding exon 4) of the NIFK gene. This alteration results from a G to A substitution at nucleotide position 458, causing the arginine (R) at amino acid position 153 to be replaced by a glutamine (Q). 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
Benign
0.28
BayesDel_addAF
Benign
-0.087
T
BayesDel_noAF
Benign
-0.27
CADD
Benign
22
DANN
Uncertain
1.0
DEOGEN2
Benign
0.20
T;T;T
Eigen
Uncertain
0.31
Eigen_PC
Uncertain
0.29
FATHMM_MKL
Uncertain
0.77
D
LIST_S2
Benign
0.81
T;T;T
M_CAP
Benign
0.013
T
MetaRNN
Benign
0.27
T;T;T
MetaSVM
Benign
-0.72
T
MutationAssessor
Uncertain
2.6
M;.;.
PrimateAI
Benign
0.32
T
PROVEAN
Uncertain
-2.5
N;N;N
REVEL
Benign
0.11
Sift
Benign
0.046
D;T;D
Sift4G
Uncertain
0.014
D;.;D
Polyphen
0.98
D;.;.
Vest4
0.45
MVP
0.89
MPC
0.21
ClinPred
0.78
D
GERP RS
5.7
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.17
gMVP
0.46

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs772093233; hg19: chr2-122488575; COSMIC: COSV53534306; COSMIC: COSV53534306; API