rs3802427

Variant names:

• chr9-34618644-C-T
• rs3802427
• NM_007234.5:c.181+32G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_007234.5(DCTN3):​c.181+32G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.176 in 1,569,298 control chromosomes in the GnomAD database, including 25,640 homozygotes. 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 0.18 (2555 hom., cov: 32)
  • Exomes 𝑓: 0.18 (23085 hom.)
• Consequence: DCTN3 NM_007234.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.290
• Publications: 11 publications found

Genes affected

DCTN3 (HGNC:2713): (dynactin subunit 3) This gene encodes the smallest 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. It is involved in a diverse array of cellular functions, including ER-to-Golgi transport, the centripetal movement of lysosomes and endosomes, spindle formation, cytokinesis, chromosome movement, nuclear positioning, and axonogenesis. This subunit, like most other dynactin subunits, exists only as a part of the dynactin complex. It is primarily an alpha-helical protein with very little coiled coil, and binds directly to the largest subunit (p150) of dynactin. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.294 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DCTN3	NM_007234.5	c.181+32G>A		intron_variant	Intron 2 of 6	ENST00000259632.12	NP_009165.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DCTN3	ENST00000259632.12	c.181+32G>A		intron_variant	Intron 2 of 6	1	NM_007234.5	ENSP00000259632.7

Frequencies

GnomAD3 genomes AF: 0.182 AC: 27650 AN: 151982 Hom.: 2557 Cov.: 32

Gnomad AFR AF: 0.196

Gnomad AMI AF: 0.240

Gnomad AMR AF: 0.225

Gnomad ASJ AF: 0.117

Gnomad EAS AF: 0.307

Gnomad SAS AF: 0.197

Gnomad FIN AF: 0.132

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.163

Gnomad OTH AF: 0.190

GnomAD2 exomes AF: 0.195 AC: 49068 AN: 251018 AF XY: 0.191

Gnomad AFR exome AF: 0.198

Gnomad AMR exome AF: 0.287

Gnomad ASJ exome AF: 0.120

Gnomad EAS exome AF: 0.318

Gnomad FIN exome AF: 0.140

Gnomad NFE exome AF: 0.165

Gnomad OTH exome AF: 0.171

GnomAD4 exome AF: 0.175 AC: 248694 AN: 1417198 Hom.: 23085 Cov.: 25 AF XY: 0.175 AC XY: 124187 AN XY: 707658

African (AFR) AF: 0.198 AC: 6438 AN: 32594

American (AMR) AF: 0.279 AC: 12449 AN: 44628

Ashkenazi Jewish (ASJ) AF: 0.117 AC: 3032 AN: 25856

East Asian (EAS) AF: 0.311 AC: 12301 AN: 39494

South Asian (SAS) AF: 0.201 AC: 17162 AN: 85296

European-Finnish (FIN) AF: 0.136 AC: 7278 AN: 53396

Middle Eastern (MID) AF: 0.174 AC: 939 AN: 5382

European-Non Finnish (NFE) AF: 0.167 AC: 179051 AN: 1071676

Other (OTH) AF: 0.171 AC: 10044 AN: 58876

GnomAD4 genome AF: 0.182 AC: 27655 AN: 152100 Hom.: 2555 Cov.: 32 AF XY: 0.182 AC XY: 13544 AN XY: 74356

African (AFR) AF: 0.196 AC: 8134 AN: 41502

American (AMR) AF: 0.226 AC: 3445 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.117 AC: 407 AN: 3470

East Asian (EAS) AF: 0.307 AC: 1586 AN: 5166

South Asian (SAS) AF: 0.196 AC: 945 AN: 4824

European-Finnish (FIN) AF: 0.132 AC: 1401 AN: 10574

Middle Eastern (MID) AF: 0.224 AC: 66 AN: 294

European-Non Finnish (NFE) AF: 0.163 AC: 11057 AN: 67978

Other (OTH) AF: 0.188 AC: 396 AN: 2110

Alfa AF: 0.166 Hom.: 1277

Bravo AF: 0.193

Asia WGS AF: 0.258 AC: 900 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.82
DANN	Benign	0.31
PhyloP100		-0.29
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3802427; hg19: chr9-34618641; COSMIC: COSV52406295; COSMIC: COSV52406295;