rs374163967
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_004082.5(DCTN1):c.2339T>C(p.Ile780Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000793 in 1,614,078 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 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. I780V) has been classified 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.2339T>C | p.Ile780Thr | missense_variant | 21/32 | ENST00000628224.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DCTN1 | ENST00000628224.3 | c.2339T>C | p.Ile780Thr | missense_variant | 21/32 | 5 | NM_004082.5 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000394 AC: 6AN: 152184Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000398 AC: 10AN: 251450Hom.: 0 AF XY: 0.0000368 AC XY: 5AN XY: 135902
GnomAD4 exome AF: 0.0000835 AC: 122AN: 1461894Hom.: 0 Cov.: 33 AF XY: 0.0000894 AC XY: 65AN XY: 727248
GnomAD4 genome ? AF: 0.0000394 AC: 6AN: 152184Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4AN XY: 74352
ClinVar
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Nov 17, 2020 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Athena Diagnostics | Jan 16, 2018 | - - |
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 | Oct 17, 2022 | This sequence change replaces isoleucine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 780 of the DCTN1 protein (p.Ile780Thr). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This missense change has been observed in individual(s) with clinical features of DCTN1-related conditions (PMID: 23881933, 31996268). ClinVar contains an entry for this variant (Variation ID: 468264). 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. 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. - |
See cases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein | Jan 28, 2021 | ACMG classification criteria: BP4 - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at