2-121736788-C-T

Variant names:

• chr2-121736788-C-T
• rs986151288
• NM_032390.5:c.63G>A

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_032390.5(NIFK):​c.63G>A​(p.Glu21Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,461,802 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: NIFK NM_032390.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.176
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP7: Synonymous conserved (PhyloP=0.176 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032390.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NIFK	NM_032390.5	MANE Select	c.63G>A	p.Glu21Glu	synonymous	Exon 1 of 7	NP_115766.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NIFK	ENST00000285814.9	TSL:1 MANE Select	c.63G>A	p.Glu21Glu	synonymous	Exon 1 of 7	ENSP00000285814.4	Q9BYG3
	NIFK	ENST00000477693.1	TSL:1	n.85G>A		non_coding_transcript_exon	Exon 1 of 4
	NIFK	ENST00000911493.1		c.63G>A	p.Glu21Glu	synonymous	Exon 1 of 7	ENSP00000581552.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000479 AC: 7 AN: 1461802 Hom.: 0 Cov.: 31 AF XY: 0.00000550 AC XY: 4 AN XY: 727206

African (AFR) AF: 0.00 AC: 0 AN: 33474

American (AMR) AF: 0.00 AC: 0 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.00000630 AC: 7 AN: 1111958

Other (OTH) AF: 0.00 AC: 0 AN: 60388

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	8.5
DANN	Benign	0.90
PhyloP100		0.18
PromoterAI		-0.0077	Neutral
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs986151288; hg19: chr2-122494364;