5-36195238-T-C
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_001085411.3(NADK2):āc.1235A>Gā(p.Asp412Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,906 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 Uncertain significance (ā ). Synonymous variant affecting the same amino acid position (i.e. D412D) has been classified as Likely benign.
Frequency
Consequence
NM_001085411.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NADK2 | NM_001085411.3 | c.1235A>G | p.Asp412Gly | missense_variant | 12/12 | ENST00000381937.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NADK2 | ENST00000381937.9 | c.1235A>G | p.Asp412Gly | missense_variant | 12/12 | 2 | NM_001085411.3 | P1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.00000400 AC: 1AN: 250214Hom.: 0 AF XY: 0.00000740 AC XY: 1AN XY: 135214
GnomAD4 exome AF: 6.85e-7 AC: 1AN: 1460906Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1AN XY: 726708
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Progressive encephalopathy with leukodystrophy due to DECR deficiency Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 30, 2023 | 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt NADK2 protein function. This variant has not been reported in the literature in individuals affected with NADK2-related conditions. This variant is present in population databases (rs772310092, gnomAD 0.003%). This sequence change replaces aspartic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 412 of the NADK2 protein (p.Asp412Gly). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at