16-23677227-G-A

Position:

• chr16-23677227-G-A

Variant summary

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

The NM_032486.4(DCTN5):​c.*10083G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0633 in 152,198 control chromosomes in the GnomAD database, including 637 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 0.063 (637 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: -0.356

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.158 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DCTN5	NM_032486.4	c.*10083G>A		3_prime_UTR_variant	6/6	ENST00000300087.7
DCTN5	NR_037573.2	n.10810G>A		non_coding_transcript_exon_variant	7/7
DCTN5	XR_001752006.3	n.8840G>A		non_coding_transcript_exon_variant	7/7
DCTN5	XR_001752007.3	n.8870G>A		non_coding_transcript_exon_variant	7/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DCTN5	ENST00000300087.7	c.*10083G>A		3_prime_UTR_variant	6/6	1	NM_032486.4	P1

Frequencies

GnomAD3 genomes AF: 0.0630 AC: 9586 AN: 152080 Hom.: 625 Cov.: 32

Gnomad AFR AF: 0.161

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0855

Gnomad ASJ AF: 0.0164

Gnomad EAS AF: 0.00885

Gnomad SAS AF: 0.0363

Gnomad FIN AF: 0.0199

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0147

Gnomad OTH AF: 0.0583

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 18 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 10

Gnomad4 EAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0633 AC: 9638 AN: 152198 Hom.: 637 Cov.: 32 AF XY: 0.0641 AC XY: 4771 AN XY: 74396

Gnomad4 AFR AF: 0.162

Gnomad4 AMR AF: 0.0858

Gnomad4 ASJ AF: 0.0164

Gnomad4 EAS AF: 0.00887

Gnomad4 SAS AF: 0.0363

Gnomad4 FIN AF: 0.0199

Gnomad4 NFE AF: 0.0147

Gnomad4 OTH AF: 0.0582

Alfa AF: 0.0409 Hom.: 34

Bravo AF: 0.0706

Asia WGS AF: 0.0620 AC: 218 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	3.2
DANN	Benign	0.57

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: rs57973275; hg19: chr16-23688548;