Variant 6-56458752-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001374736.1(DST):c.*253C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0316 in 321,888 control chromosomes in the GnomAD database, including 219 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.029 ( 81 hom., cov: 32)

Exomes 𝑓: 0.034 ( 138 hom. )

Consequence

DST
NM_001374736.1 3_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.485

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 6-56458752-G-T is Benign according to our data. Variant chr6-56458752-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 1300301.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0294 (4466/152158) while in subpopulation NFE AF= 0.0423 (2875/68000). AF 95% confidence interval is 0.041. There are 81 homozygotes in gnomad4. There are 2001 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 81 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DST	NM_001374736.1 linkuse as main transcript	c.*253C>A		3_prime_UTR_variant	104/104	ENST00000680361.1	NP_001361665.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DST	ENST00000680361.1 linkuse as main transcript	c.*253C>A		3_prime_UTR_variant	104/104		NM_001374736.1	ENSP00000505098

Frequencies

GnomAD3 genomes

AF:

0.0293

AC:

4461

AN:

152040

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0233

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0145

Gnomad ASJ

AF:

0.0478

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.0157

Gnomad FIN

AF:

0.00963

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0423

Gnomad OTH

AF:

0.0263

GnomAD4 exome

AF:

0.0336

AC:

5697

AN:

169730

Hom.:

138

Cov.:

AF XY:

0.0330

AC XY:

2857

AN XY:

86642

show subpopulations

Gnomad4 AFR exome

AF:

0.0250

Gnomad4 AMR exome

AF:

0.0178

Gnomad4 ASJ exome

AF:

0.0455

Gnomad4 EAS exome

AF:

0.0000747

Gnomad4 SAS exome

AF:

0.0160

Gnomad4 FIN exome

AF:

0.0146

Gnomad4 NFE exome

AF:

0.0410

Gnomad4 OTH exome

AF:

0.0355

GnomAD4 genome

AF:

0.0294

AC:

4466

AN:

152158

Hom.:

Cov.:

AF XY:

0.0269

AC XY:

2001

AN XY:

74382

show subpopulations

Gnomad4 AFR

AF:

0.0233

Gnomad4 AMR

AF:

0.0145

Gnomad4 ASJ

AF:

0.0478

Gnomad4 EAS

AF:

0.000387

Gnomad4 SAS

AF:

0.0158

Gnomad4 FIN

AF:

0.00963

Gnomad4 NFE

AF:

0.0423

Gnomad4 OTH

AF:

0.0261

Alfa

AF:

0.0272

Hom.:

Bravo

AF:

0.0297

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 28, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

1.8

DANN

Benign

0.52

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over