4-163129043-C-T
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_138386.3(NAF1):c.1339G>A(p.Val447Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000389 in 1,106,108 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. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_138386.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -8 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
NAF1 | ENST00000274054.3 | c.1339G>A | p.Val447Ile | missense_variant | Exon 8 of 8 | 1 | NM_138386.3 | ENSP00000274054.2 | ||
NAF1 | ENST00000422287.6 | c.1034-1928G>A | intron_variant | Intron 7 of 7 | 1 | ENSP00000408963.2 | ||||
NAF1 | ENST00000509434.5 | c.114+8156G>A | intron_variant | Intron 2 of 2 | 3 | ENSP00000427518.1 | ||||
NAF1 | ENST00000509884.1 | n.*77G>A | downstream_gene_variant | 5 |
Frequencies
GnomAD3 genomes AF: 0.0000599 AC: 4AN: 66792Hom.: 0 Cov.: 14
GnomAD3 exomes AF: 0.0000136 AC: 2AN: 147510Hom.: 0 AF XY: 0.0000125 AC XY: 1AN XY: 79694
GnomAD4 exome AF: 0.0000375 AC: 39AN: 1039316Hom.: 0 Cov.: 30 AF XY: 0.0000350 AC XY: 18AN XY: 513750
GnomAD4 genome AF: 0.0000599 AC: 4AN: 66792Hom.: 0 Cov.: 14 AF XY: 0.0000992 AC XY: 3AN XY: 30230
ClinVar
Submissions by phenotype
not provided Uncertain:1
This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 447 of the NAF1 protein (p.Val447Ile). This variant is present in population databases (no rsID available, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with NAF1-related conditions. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at