rs754702783

Variant names:

• chr9-128063658-C-A
• rs754702783
• NM_197956.4:c.754G>T

Your query was ambiguous. Multiple possible variants found:

• chr9-128063658-C-A
• chr9-128063658-C-T

Variant summary

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

The NM_197956.4(NAIF1):​c.754G>T​(p.Asp252Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000821 in 1,461,786 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. D252N) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000082 (0 hom.)
• Consequence: NAIF1 NM_197956.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.38

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NAIF1	NM_197956.4	c.754G>T	p.Asp252Tyr	missense_variant	Exon 2 of 2	ENST00000373078.5	NP_931045.1
NAIF1	XM_047422940.1	c.754G>T	p.Asp252Tyr	missense_variant	Exon 2 of 3		XP_047278896.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NAIF1	ENST00000373078.5	c.754G>T	p.Asp252Tyr	missense_variant	Exon 2 of 2	1	NM_197956.4	ENSP00000362170.4
NAIF1	ENST00000470245.1	n.85G>T		non_coding_transcript_exon_variant	Exon 1 of 2	1
NAIF1	ENST00000488519.1	n.381G>T		non_coding_transcript_exon_variant	Exon 2 of 2	1
NAIF1	ENST00000466139.1	n.327G>T		non_coding_transcript_exon_variant	Exon 2 of 2	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000821 AC: 12 AN: 1461786 Hom.: 0 Cov.: 31 AF XY: 0.00000550 AC XY: 4 AN XY: 727194

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000302

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.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.80
BayesDel_addAF	Uncertain	0.077	D
BayesDel_noAF	Benign	-0.13
CADD	Pathogenic	30
DANN	Uncertain	1.0
DEOGEN2	Benign	0.15	T
Eigen	Uncertain	0.53
Eigen_PC	Uncertain	0.59
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.0060	T
MetaRNN	Uncertain	0.56	D
MetaSVM	Benign	-0.44	T
MutationAssessor	Benign	1.5	L
PrimateAI	Uncertain	0.76	T
PROVEAN	Uncertain	-3.1	D
REVEL	Uncertain	0.46
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0030	D
Polyphen		0.74	P
Vest4		0.65
MutPred		0.31		Loss of disorder (P = 0.032);
MVP		0.33
MPC		2.1
ClinPred		0.99	D
GERP RS		5.3
Varity_R		0.50
gMVP		0.54

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: rs754702783; hg19: chr9-130825937;