chr6-56458752-G-A

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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=-0.84).
• 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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DST	NM_001374736.1	c.*253C>T		3_prime_UTR_variant	Exon 104 of 104	ENST00000680361.1	NP_001361665.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DST	ENST00000680361	c.*253C>T		3_prime_UTR_variant	Exon 104 of 104		NM_001374736.1	ENSP00000505098.1

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

Gnomad4 AFR exome AF: 0.000897

Gnomad4 AMR exome AF: 0.00542

Gnomad4 ASJ exome AF: 0.00961

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000522

Gnomad4 FIN exome AF: 0.000960

Gnomad4 NFE exome AF: 0.00613

Gnomad4 OTH exome AF: 0.00518

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

Gnomad4 AFR AF: 0.00118

Gnomad4 AMR AF: 0.00714

Gnomad4 ASJ AF: 0.0101

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000415

Gnomad4 FIN AF: 0.000661

Gnomad4 NFE AF: 0.00587

Gnomad4 OTH AF: 0.00616

Alfa AF: 0.000469 Hom.: 25

Bravo AF: 0.00521

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.8
DANN	Benign	0.73
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs79455288; hg19: chr6-56323550;