rs12447304

Positions:

• chr16-23670950-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_032486.4(DCTN5):​c.*3806C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0559 in 152,296 control chromosomes in the GnomAD database, including 371 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 0.056 (371 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: DCTN5 NM_032486.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.199

Genes affected

DCTN5 (HGNC:24594): (dynactin subunit 5) This gene encodes a subunit of dynactin, a component of the cytoplasmic dynein motor machinery involved in minus-end-directed transport. The encoded protein is a component of the pointed-end subcomplex and is thought to bind membranous cargo. A pseudogene of this gene is located on the long arm of chromosome 1. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Jan 2011]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0884 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DCTN5	NM_032486.4	c.*3806C>G		3_prime_UTR_variant	6/6	ENST00000300087.7	NP_115875.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DCTN5	ENST00000300087.7	c.*3806C>G		3_prime_UTR_variant	6/6	1	NM_032486.4	ENSP00000300087	P1
	ENST00000566996.2	n.940C>G		non_coding_transcript_exon_variant	1/2	2

Frequencies

GnomAD3 genomes AF: 0.0559 AC: 8505 AN: 152178 Hom.: 371 Cov.: 32

Gnomad AFR AF: 0.0163

Gnomad AMI AF: 0.0548

Gnomad AMR AF: 0.0921

Gnomad ASJ AF: 0.0251

Gnomad EAS AF: 0.000384

Gnomad SAS AF: 0.0327

Gnomad FIN AF: 0.0374

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0824

Gnomad OTH AF: 0.0569

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 16 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 6

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.0559 AC: 8508 AN: 152296 Hom.: 371 Cov.: 32 AF XY: 0.0531 AC XY: 3951 AN XY: 74464

Gnomad4 AFR AF: 0.0163

Gnomad4 AMR AF: 0.0924

Gnomad4 ASJ AF: 0.0251

Gnomad4 EAS AF: 0.000385

Gnomad4 SAS AF: 0.0325

Gnomad4 FIN AF: 0.0374

Gnomad4 NFE AF: 0.0824

Gnomad4 OTH AF: 0.0563

Alfa AF: 0.0652 Hom.: 62

Bravo AF: 0.0629

Asia WGS AF: 0.0180 AC: 64 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	4.8
DANN	Benign	0.67

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

Publications

LitVar

Other links and lift over

dbSNP: rs12447304; hg19: chr16-23682271;