rs10096097

Positions:

• chr8-30169582-G-A

Variant summary

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

The NM_006571.4(DCTN6):​c.88+5407G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.618 in 152,068 control chromosomes in the GnomAD database, including 30,707 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 0.62 (30707 hom., cov: 32)
• Consequence: DCTN6 NM_006571.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.170

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.726 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DCTN6	NM_006571.4	c.88+5407G>A		intron_variant		ENST00000221114.8	NP_006562.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DCTN6	ENST00000221114.8	c.88+5407G>A		intron_variant		1	NM_006571.4	ENSP00000221114	P1

Frequencies

GnomAD3 genomes AF: 0.618 AC: 93962 AN: 151950 Hom.: 30709 Cov.: 32

Gnomad AFR AF: 0.435

Gnomad AMI AF: 0.808

Gnomad AMR AF: 0.636

Gnomad ASJ AF: 0.769

Gnomad EAS AF: 0.241

Gnomad SAS AF: 0.565

Gnomad FIN AF: 0.715

Gnomad MID AF: 0.753

Gnomad NFE AF: 0.732

Gnomad OTH AF: 0.645

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

GnomAD4 genome AF: 0.618 AC: 93963 AN: 152068 Hom.: 30707 Cov.: 32 AF XY: 0.616 AC XY: 45754 AN XY: 74328

Gnomad4 AFR AF: 0.434

Gnomad4 AMR AF: 0.636

Gnomad4 ASJ AF: 0.769

Gnomad4 EAS AF: 0.241

Gnomad4 SAS AF: 0.564

Gnomad4 FIN AF: 0.715

Gnomad4 NFE AF: 0.732

Gnomad4 OTH AF: 0.642

Alfa AF: 0.708 Hom.: 36469

Bravo AF: 0.603

Asia WGS AF: 0.429 AC: 1493 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	4.4
DANN	Benign	0.84

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: rs10096097; hg19: chr8-30027098;