rs6906792

Positions:

• chr6-56538978-T-G

Variant summary

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

The NM_001374736.1(DST):​c.16609-2038A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.658 in 151,914 control chromosomes in the GnomAD database, including 33,456 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 0.66 (33456 hom., cov: 31)
• Consequence: DST NM_001374736.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.496

Genes affected

DST (HGNC:1090): (dystonin) This gene encodes a member of the plakin protein family of adhesion junction plaque proteins. Multiple alternatively spliced transcript variants encoding distinct isoforms have been found for this gene, but the full-length nature of some variants has not been defined. It has been reported that some isoforms are expressed in neural and muscle tissue, anchoring neural intermediate filaments to the actin cytoskeleton, and some isoforms are expressed in epithelial tissue, anchoring keratin-containing intermediate filaments to hemidesmosomes. Consistent with the expression, mice defective for this gene show skin blistering and neurodegeneration. [provided by RefSeq, Mar 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.7 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DST	NM_001374736.1	c.16609-2038A>C		intron_variant		ENST00000680361.1	NP_001361665.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DST	ENST00000680361.1	c.16609-2038A>C		intron_variant			NM_001374736.1	ENSP00000505098

Frequencies

GnomAD3 genomes AF: 0.658 AC: 99887 AN: 151794 Hom.: 33427 Cov.: 31

Gnomad AFR AF: 0.545

Gnomad AMI AF: 0.560

Gnomad AMR AF: 0.672

Gnomad ASJ AF: 0.584

Gnomad EAS AF: 0.664

Gnomad SAS AF: 0.655

Gnomad FIN AF: 0.818

Gnomad MID AF: 0.570

Gnomad NFE AF: 0.705

Gnomad OTH AF: 0.623

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

GnomAD4 genome AF: 0.658 AC: 99966 AN: 151914 Hom.: 33456 Cov.: 31 AF XY: 0.662 AC XY: 49148 AN XY: 74260

Gnomad4 AFR AF: 0.545

Gnomad4 AMR AF: 0.672

Gnomad4 ASJ AF: 0.584

Gnomad4 EAS AF: 0.664

Gnomad4 SAS AF: 0.656

Gnomad4 FIN AF: 0.818

Gnomad4 NFE AF: 0.705

Gnomad4 OTH AF: 0.625

Alfa AF: 0.683 Hom.: 4451

Bravo AF: 0.640

Asia WGS AF: 0.655 AC: 2275 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.7
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: rs6906792; hg19: chr6-56403776;