9-128067095-C-T

Variant names:

• chr9-128067095-C-T
• rs146217741
• NM_197956.4:c.7G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_197956.4(NAIF1):​c.7G>A​(p.Val3Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000278 in 1,440,932 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. V3F) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0000028 (0 hom.)
• Consequence: NAIF1 NM_197956.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.09
• Publications: 0 publications found

Genes affected

NAIF1 (HGNC:25446): (nuclear apoptosis inducing factor 1) Involved in negative regulation of cell growth and regulation of mitochondrial membrane permeability involved in apoptotic process. Located in cytosol; nucleoplasm; and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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=0.07018289).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_197956.4. 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
	NAIF1	NM_197956.4	MANE Select	c.7G>A	p.Val3Ile	missense	Exon 1 of 2	NP_931045.1	Q69YI7-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NAIF1	ENST00000373078.5	TSL:1 MANE Select	c.7G>A	p.Val3Ile	missense	Exon 1 of 2	ENSP00000362170.4	Q69YI7-1
	NAIF1	ENST00000466139.1	TSL:3	n.84+1028G>A		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD2 exomes AF: 0.0000122 AC: 3 AN: 245008 AF XY: 0.00000755

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000164

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000278 AC: 4 AN: 1440932 Hom.: 0 Cov.: 36 AF XY: 0.00000281 AC XY: 2 AN XY: 712894

African (AFR) AF: 0.00 AC: 0 AN: 32976

American (AMR) AF: 0.00 AC: 0 AN: 43636

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25418

East Asian (EAS) AF: 0.0000765 AC: 3 AN: 39200

South Asian (SAS) AF: 0.0000117 AC: 1 AN: 85266

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52714

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5694

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1096674

Other (OTH) AF: 0.00 AC: 0 AN: 59354

GnomAD4 genome Cov.: 34

ExAC AF: 0.0000165 AC: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.020	T
Eigen	Benign	-0.098
Eigen_PC	Benign	0.092
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.86	D
M_CAP	Benign	0.0022	T
MetaRNN	Benign	0.070	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N
PhyloP100		1.1
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-0.32	N
REVEL	Benign	0.045
Sift	Benign	0.13	T
Sift4G	Benign	0.20	T
Polyphen		0.43	B
Vest4		0.076
MutPred		0.18		Loss of MoRF binding (P = 0.237)
MVP		0.35
MPC		0.69
ClinPred		0.17	T
GERP RS		5.0
PromoterAI		-0.18	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.12
gMVP		0.25
Mutation Taster		=95/5	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: rs146217741; hg19: chr9-130829374;