rs1274754432
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_004082.5(DCTN1):c.3254G>A(p.Gly1085Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000062 in 1,612,438 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_004082.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DCTN1 | NM_004082.5 | c.3254G>A | p.Gly1085Glu | missense_variant | 28/32 | ENST00000628224.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DCTN1 | ENST00000628224.3 | c.3254G>A | p.Gly1085Glu | missense_variant | 28/32 | 5 | NM_004082.5 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152192Hom.: 0 Cov.: 32
GnomAD4 exome AF: 0.00000548 AC: 8AN: 1460246Hom.: 0 Cov.: 32 AF XY: 0.00000688 AC XY: 5AN XY: 726300
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152192Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74338
ClinVar
Submissions by phenotype
Neuronopathy, distal hereditary motor, type 7B;C1862939:Amyotrophic lateral sclerosis type 1;C1868594:Perry syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 02, 2024 | This sequence change replaces glycine, which is neutral and non-polar, with glutamic acid, which is acidic and polar, at codon 1085 of the DCTN1 protein (p.Gly1085Glu). This variant is present in population databases (no rsID available, gnomAD 0.0008%). This variant has not been reported in the literature in individuals affected with DCTN1-related conditions. ClinVar contains an entry for this variant (Variation ID: 536151). 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 not expected to disrupt DCTN1 protein function with a negative 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