rs142030960
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Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP7BS2
The NM_004082.5(DCTN1):c.3498G>T(p.Thr1166=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000992 in 1,613,494 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000010 ( 0 hom. )
Consequence
DCTN1
NM_004082.5 synonymous
NM_004082.5 synonymous
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 0.0510
Genes affected
DCTN1 (HGNC:2711): (dynactin subunit 1) This gene encodes the largest subunit of dynactin, a macromolecular complex consisting of 10 subunits ranging in size from 22 to 150 kD. Dynactin binds to both microtubules and cytoplasmic dynein. Dynactin is involved in a diverse array of cellular functions, including ER-to-Golgi transport, the centripetal movement of lysosomes and endosomes, spindle formation, chromosome movement, nuclear positioning, and axonogenesis. This subunit interacts with dynein intermediate chain by its domains directly binding to dynein and binds to microtubules via a highly conserved glycine-rich cytoskeleton-associated protein (CAP-Gly) domain in its N-terminus. Alternative splicing of this gene results in multiple transcript variants encoding distinct isoforms. Mutations in this gene cause distal hereditary motor neuronopathy type VIIB (HMN7B) which is also known as distal spinal and bulbar muscular atrophy (dSBMA). [provided by RefSeq, Oct 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -9 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.64).
BP7
Synonymous conserved (PhyloP=0.051 with no splicing effect.
BS2
High AC in GnomAdExome4 at 15 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
DCTN1 | NM_004082.5 | c.3498G>T | p.Thr1166= | synonymous_variant | 29/32 | ENST00000628224.3 | NP_004073.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
DCTN1 | ENST00000628224.3 | c.3498G>T | p.Thr1166= | synonymous_variant | 29/32 | 5 | NM_004082.5 | ENSP00000487279 | A1 |
Frequencies
GnomAD3 genomes AF: 0.00000658 AC: 1AN: 152070Hom.: 0 Cov.: 32
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GnomAD4 exome AF: 0.0000103 AC: 15AN: 1461424Hom.: 0 Cov.: 32 AF XY: 0.00000688 AC XY: 5AN XY: 726982
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GnomAD4 genome AF: 0.00000658 AC: 1AN: 152070Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74292
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ClinVar
Not reported inComputational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at