chr2-121736767-C-A

Position:

• chr2-121736767-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_032390.5(NIFK):​c.84G>T​(p.Gln28His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,738 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: NIFK NM_032390.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.18

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 (HGNC:):

ACMG classification

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=0.18588719).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NIFK	NM_032390.5	c.84G>T	p.Gln28His	missense_variant	1/7	ENST00000285814.9	NP_115766.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NIFK	ENST00000285814.9	c.84G>T	p.Gln28His	missense_variant	1/7	1	NM_032390.5	ENSP00000285814.4
NIFK	ENST00000477693.1	n.106G>T		non_coding_transcript_exon_variant	1/4	1
NIFK	ENST00000451734.1	c.84G>T	p.Gln28His	missense_variant	1/5	3		ENSP00000398116.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461738 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727170

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000224

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 27, 2024

The c.84G>T (p.Q28H) alteration is located in exon 1 (coding exon 1) of the NIFK gene. This alteration results from a G to T substitution at nucleotide position 84, causing the glutamine (Q) at amino acid position 28 to be replaced by a histidine (H). 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	0.16
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.056	T;T
Eigen	Benign	-0.51
Eigen_PC	Benign	-0.80
FATHMM_MKL	Benign	0.036	N
LIST_S2	Benign	0.52	T;T
M_CAP	Benign	0.0049	T
MetaRNN	Benign	0.19	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	L;.
PrimateAI	Benign	0.28	T
PROVEAN	Uncertain	-2.4	N;D
REVEL	Benign	0.055
Sift	Uncertain	0.011	D;D
Sift4G	Uncertain	0.015	D;D
Polyphen		1.0	D;.
Vest4		0.22
MutPred		0.29		Loss of ubiquitination at K24 (P = 0.077);Loss of ubiquitination at K24 (P = 0.077);
MVP		0.60
MPC		0.11
ClinPred		0.72	D
GERP RS		-2.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.16
gMVP		0.37

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

Other links and lift over

dbSNP: rs570833395; hg19: chr2-122494343;