chr8-30158242-C-T

Variant names:

• chr8-30158242-C-T
• rs10503862
• NM_006571.4:c.23+1836C>T

Variant summary

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

The NM_006571.4(DCTN6):​c.23+1836C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0126 in 152,190 control chromosomes in the GnomAD database, including 40 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 0.013 (40 hom., cov: 32)
• Consequence: DCTN6 NM_006571.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.07
• Publications: 1 publications found

Genes affected

DCTN6 (HGNC:16964): (dynactin subunit 6) The protein encoded by this gene contains an RGD (Arg-Gly-Asp) motif in the N-terminal region, which confers adhesive properties to macromolecular proteins like fibronectin. It shares a high degree of sequence similarity with the mouse homolog, which has been suggested to play a role in mitochondrial biogenesis. The exact biological function of this gene is not known. [provided by RefSeq, Jul 2008]

LEPROTL1 (HGNC:6555): (leptin receptor overlapping transcript like 1) Enables identical protein binding activity. Predicted to be involved in late endosome to vacuole transport via multivesicular body sorting pathway and negative regulation of growth hormone receptor signaling pathway. Predicted to be integral component of membrane. Predicted to be active in endosome. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000305693 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0501 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DCTN6	NM_006571.4	c.23+1836C>T		intron_variant	Intron 1 of 6	ENST00000221114.8	NP_006562.1
LOC124901927	XR_007060880.1	n.-132G>A		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DCTN6	ENST00000221114.8	c.23+1836C>T		intron_variant	Intron 1 of 6	1	NM_006571.4	ENSP00000221114.3

Frequencies

GnomAD3 genomes AF: 0.0126 AC: 1914 AN: 152072 Hom.: 40 Cov.: 32

Gnomad AFR AF: 0.00251

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0369

Gnomad ASJ AF: 0.00433

Gnomad EAS AF: 0.0550

Gnomad SAS AF: 0.0131

Gnomad FIN AF: 0.0272

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00836

Gnomad OTH AF: 0.0124

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0126 AC: 1917 AN: 152190 Hom.: 40 Cov.: 32 AF XY: 0.0142 AC XY: 1059 AN XY: 74396

African (AFR) AF: 0.00251 AC: 104 AN: 41502

American (AMR) AF: 0.0370 AC: 565 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00433 AC: 15 AN: 3468

East Asian (EAS) AF: 0.0553 AC: 287 AN: 5188

South Asian (SAS) AF: 0.0131 AC: 63 AN: 4822

European-Finnish (FIN) AF: 0.0272 AC: 288 AN: 10578

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00836 AC: 569 AN: 68028

Other (OTH) AF: 0.0123 AC: 26 AN: 2116

Alfa AF: 0.0141 Hom.: 17

Bravo AF: 0.0147

Asia WGS AF: 0.0210 AC: 73 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	7.1
DANN	Benign	0.83
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism

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: rs10503862; hg19: chr8-30015758;