NM_001374736.1:c.13722-547A>G

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 publications found

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]

DST Gene-Disease associations (from GenCC):

• hereditary sensory and autonomic neuropathy type 6

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE, LIMITED Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), Orphanet, G2P, Ambry Genetics
• epidermolysis bullosa simplex 3, localized or generalized intermediate, with BP230 deficiency

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Ambry Genetics, Orphanet

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001374736.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DST	NM_001374736.1	MANE Select	c.13722-547A>G		intron	N/A	NP_001361665.1	A0A7P0T890
	DST	NM_001374734.1		c.13749-547A>G		intron	N/A	NP_001361663.1
	DST	NM_001374722.1		c.13722-547A>G		intron	N/A	NP_001361651.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DST	ENST00000680361.1	MANE Select	c.13722-547A>G		intron	N/A	ENSP00000505098.1	A0A7P0T890
	DST	ENST00000244364.10	TSL:1	c.5853-547A>G		intron	N/A	ENSP00000244364.6	Q03001-8
	DST	ENST00000361203.7	TSL:5	c.13089-547A>G		intron	N/A	ENSP00000354508.3	F8W9J4

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

African (AFR) AF: 0.525 AC: 21731 AN: 41398

American (AMR) AF: 0.108 AC: 1647 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0876 AC: 304 AN: 3470

East Asian (EAS) AF: 0.188 AC: 971 AN: 5166

South Asian (SAS) AF: 0.0752 AC: 362 AN: 4816

European-Finnish (FIN) AF: 0.0431 AC: 457 AN: 10596

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.0756 AC: 5140 AN: 67988

Other (OTH) AF: 0.149 AC: 315 AN: 2108

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.0
DANN	Benign	0.59
PhyloP100		0.31
Mutation Taster		=100/0	polymorphism (auto)

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: rs973089; hg19: chr6-56435357;