2-15467670-A-C
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_015909.4(NBAS):āc.2012T>Gā(p.Phe671Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000157 in 1,612,042 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_015909.4 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.000164 AC: 25AN: 152186Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000760 AC: 19AN: 250072Hom.: 0 AF XY: 0.0000814 AC XY: 11AN XY: 135144
GnomAD4 exome AF: 0.000156 AC: 228AN: 1459856Hom.: 0 Cov.: 30 AF XY: 0.000187 AC XY: 136AN XY: 726272
GnomAD4 genome AF: 0.000164 AC: 25AN: 152186Hom.: 0 Cov.: 33 AF XY: 0.000175 AC XY: 13AN XY: 74344
ClinVar
Submissions by phenotype
Short stature-optic atrophy-Pelger-HuC+t anomaly syndrome Uncertain:2
- -
The observed missense variant c.2012T>G(p.Phe671Cys) in NBAS gene has been reported previously in an individual with mitochondrial disorders (Staufner C, et al., 2020). The c.2012T>G variant has 0.01% allele frequency in gnomAD Exomes. This variant has been reported to the ClinVar database as Uncertain Significance. The amino acid Phenylalanine at position 671 is changed to a Cysteine changing protein sequence and it might alter its composition and physico-chemical properties. Multiple lines of computational evidence (Polyphen-probabaly damaging, SIFT-damaging and Mutation Taster-disease causing) predict a damaging effect on protein structure and function for this variant.The reference amino acid p.Phe671Cys in NBAS is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. For these reasons, this variant has been classified as Uncertain Significance. A different variant in NBAS gene has been found in the spouse Mr. NCGM ID: 30507801448 in heterozygous state. -
not provided Uncertain:1Benign:1
In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 31589614, 34490615, 31761904) -
- -
Short stature-optic atrophy-Pelger-HuC+t anomaly syndrome;C3809651:Infantile liver failure syndrome 2 Uncertain:1
- -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at