dbSNP rs370998435: NIFK:p.Arg288Pro (chr2-121727743-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_032390.5(NIFK):c.863G>C(p.Arg288Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,447,338 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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. R288Q) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

NIFK
NM_032390.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.175

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]

NIFK links:

NIFK-AS1 (HGNC:27385): (NIFK antisense RNA 1)

NIFK-AS1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.08993325).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NIFK	NM_032390.5 link	c.863G>C	p.Arg288Pro	missense_variant	Exon 7 of 7	ENST00000285814.9	NP_115766.3	Q9BYG3
NIFK-AS1	NR_037857.1 link	n.1084-60C>G		intron_variant	Intron 3 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NIFK	ENST00000285814.9 link	c.863G>C	p.Arg288Pro	missense_variant	Exon 7 of 7	1	NM_032390.5	ENSP00000285814.4		Q9BYG3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000420

AC:

AN:

238320

Hom.:

AF XY:

0.00000777

AC XY:

AN XY:

128650

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000569

Gnomad SAS 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:

0.00000138

AC:

AN:

1447338

Hom.:

Cov.:

AF XY:

0.00000139

AC XY:

AN XY:

719536

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.0097

T;T

Eigen

Benign

-0.34

Eigen_PC

Benign

-0.48

FATHMM_MKL

Benign

0.44

LIST_S2

Benign

0.68

T;T

M_CAP

Benign

0.0040

MetaRNN

Benign

0.090

T;T

MetaSVM

Benign

-0.95

MutationAssessor

Uncertain

2.1

M;.

PrimateAI

Benign

0.23

PROVEAN

Benign

-1.2

N;N

REVEL

Benign

0.069

Sift

Uncertain

0.018

D;D

Sift4G

Benign

0.12

T;T

Polyphen

0.93

P;.

Vest4

0.34

MutPred

0.18

Gain of glycosylation at R288 (P = 0.004);.;

MVP

0.66

MPC

0.17

ClinPred

0.36

GERP RS

-0.33

Varity_R

0.20

gMVP

0.078

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

LitVar

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

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over