chr6-15523067-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_032122.5(DTNBP1):c.964G>A(p.Asp322Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000415 in 1,614,072 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D322E) has been classified as Uncertain significance.
Frequency
Consequence
NM_032122.5 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DTNBP1 | NM_032122.5 | c.964G>A | p.Asp322Asn | missense_variant | 10/10 | ENST00000344537.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DTNBP1 | ENST00000344537.10 | c.964G>A | p.Asp322Asn | missense_variant | 10/10 | 1 | NM_032122.5 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000854 AC: 13AN: 152178Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000115 AC: 29AN: 251488Hom.: 0 AF XY: 0.0000736 AC XY: 10AN XY: 135920
GnomAD4 exome AF: 0.0000369 AC: 54AN: 1461894Hom.: 0 Cov.: 31 AF XY: 0.0000399 AC XY: 29AN XY: 727248
GnomAD4 genome AF: 0.0000854 AC: 13AN: 152178Hom.: 0 Cov.: 33 AF XY: 0.0000538 AC XY: 4AN XY: 74344
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 15, 2022 | The c.964G>A (p.D322N) alteration is located in exon 10 (coding exon 10) of the DTNBP1 gene. This alteration results from a G to A substitution at nucleotide position 964, causing the aspartic acid (D) at amino acid position 322 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 18, 2023 | This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 322 of the DTNBP1 protein (p.Asp322Asn). This variant is present in population databases (rs368759511, gnomAD 0.05%). This variant has not been reported in the literature in individuals affected with DTNBP1-related conditions. ClinVar contains an entry for this variant (Variation ID: 2077798). 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 DTNBP1 protein function with a positive predictive value of 80%. 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