6-56570559-T-C

Variant names:

• chr6-56570559-T-C
• rs973089
• NM_001374736.1:c.13722-547A>G

Variant summary

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

The NM_001374736.1(DST):​c.13722-547A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.204 in 152,026 control chromosomes in the GnomAD database, including 6,209 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 0.20 (6209 hom., cov: 31)
• Consequence: DST NM_001374736.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.308

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.519 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DST	NM_001374736.1	c.13722-547A>G		intron_variant	Intron 53 of 103	ENST00000680361.1	NP_001361665.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DST	ENST00000680361.1	c.13722-547A>G		intron_variant	Intron 53 of 103		NM_001374736.1	ENSP00000505098.1

Frequencies

GnomAD3 genomes AF: 0.203 AC: 30877 AN: 151908 Hom.: 6179 Cov.: 31

Gnomad AFR AF: 0.524

Gnomad AMI AF: 0.0121

Gnomad AMR AF: 0.108

Gnomad ASJ AF: 0.0876

Gnomad EAS AF: 0.188

Gnomad SAS AF: 0.0753

Gnomad FIN AF: 0.0431

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0756

Gnomad OTH AF: 0.151

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

GnomAD4 genome AF: 0.204 AC: 30960 AN: 152026 Hom.: 6209 Cov.: 31 AF XY: 0.198 AC XY: 14704 AN XY: 74326

Gnomad4 AFR AF: 0.525

Gnomad4 AMR AF: 0.108

Gnomad4 ASJ AF: 0.0876

Gnomad4 EAS AF: 0.188

Gnomad4 SAS AF: 0.0752

Gnomad4 FIN AF: 0.0431

Gnomad4 NFE AF: 0.0756

Gnomad4 OTH AF: 0.149

Alfa AF: 0.0647 Hom.: 158

Bravo AF: 0.224

Asia WGS AF: 0.171 AC: 594 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.0
DANN	Benign	0.59

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: rs973089; hg19: chr6-56435357;