rs79455288

Variant names:

• chr6-56458752-G-A
• rs79455288
• NM_001374736.1:c.*253C>T

Your query was ambiguous. Multiple possible variants found:

• chr6-56458752-G-A
• chr6-56458752-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001374736.1(DST):​c.*253C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00453 in 321,980 control chromosomes in the GnomAD database, including 9 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 0.0040 (3 hom., cov: 32)
  • Exomes 𝑓: 0.0050 (6 hom.)
• Consequence: DST NM_001374736.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.485
• Publications: 2 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=-0.84).
• BS1: Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.00404 (614/152168) while in subpopulation AMR AF = 0.00714 (109/15276). AF 95% confidence interval is 0.00605. There are 3 homozygotes in GnomAd4. There are 278 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 3 AR gene

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.*253C>T		3_prime_UTR	Exon 104 of 104	NP_001361665.1	A0A7P0T890
	DST	NM_001374734.1		c.*253C>T		3_prime_UTR	Exon 103 of 103	NP_001361663.1
	DST	NM_001374722.1		c.*253C>T		3_prime_UTR	Exon 103 of 103	NP_001361651.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DST	ENST00000680361.1	MANE Select	c.*253C>T		3_prime_UTR	Exon 104 of 104	ENSP00000505098.1	A0A7P0T890
	DST	ENST00000244364.10	TSL:1	c.*253C>T		3_prime_UTR	Exon 84 of 84	ENSP00000244364.6	Q03001-8
	DST	ENST00000523292.5	TSL:1	c.*253C>T		3_prime_UTR	Exon 5 of 5	ENSP00000431020.1	H0YC65

Frequencies

GnomAD3 genomes AF: 0.00404 AC: 614 AN: 152050 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.00118

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00714

Gnomad ASJ AF: 0.0101

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.000661

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00587

Gnomad OTH AF: 0.00623

GnomAD4 exome AF: 0.00498 AC: 846 AN: 169812 Hom.: 6 Cov.: 3 AF XY: 0.00523 AC XY: 453 AN XY: 86684

African (AFR) AF: 0.000897 AC: 5 AN: 5574

American (AMR) AF: 0.00542 AC: 36 AN: 6644

Ashkenazi Jewish (ASJ) AF: 0.00961 AC: 60 AN: 6242

East Asian (EAS) AF: 0.00 AC: 0 AN: 13394

South Asian (SAS) AF: 0.000522 AC: 4 AN: 7666

European-Finnish (FIN) AF: 0.000960 AC: 8 AN: 8334

Middle Eastern (MID) AF: 0.00118 AC: 1 AN: 850

European-Non Finnish (NFE) AF: 0.00613 AC: 676 AN: 110294

Other (OTH) AF: 0.00518 AC: 56 AN: 10814

GnomAD4 genome AF: 0.00404 AC: 614 AN: 152168 Hom.: 3 Cov.: 32 AF XY: 0.00374 AC XY: 278 AN XY: 74384

African (AFR) AF: 0.00118 AC: 49 AN: 41518

American (AMR) AF: 0.00714 AC: 109 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.0101 AC: 35 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4822

European-Finnish (FIN) AF: 0.000661 AC: 7 AN: 10590

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

European-Non Finnish (NFE) AF: 0.00587 AC: 399 AN: 68004

Other (OTH) AF: 0.00616 AC: 13 AN: 2110

Alfa AF: 0.000457 Hom.: 26

Bravo AF: 0.00521

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.8
DANN	Benign	0.73
PhyloP100		0.48
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs79455288; hg19: chr6-56323550;