Variant rs137865390 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7

The NM_001723.7(DST):c.84T>C(p.Asn28=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00106 in 1,614,142 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00084 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0011 ( 0 hom. )

Consequence

DST
NM_001723.7 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.68

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 Likely_benign. Variant got -5 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.64).

BP6

Variant 6-56642705-A-G is Benign according to our data. Variant chr6-56642705-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 474556.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr6-56642705-A-G is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=1.68 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DST	NM_001723.7 linkuse as main transcript	c.84T>C	p.Asn28=	synonymous_variant	1/24	ENST00000370765.11	NP_001714.1
DST	NM_001374736.1 linkuse as main transcript	c.1779-202T>C		intron_variant		ENST00000680361.1	NP_001361665.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DST	ENST00000370765.11 linkuse as main transcript	c.84T>C	p.Asn28=	synonymous_variant	1/24	1	NM_001723.7	ENSP00000359801		Q03001-3
DST	ENST00000680361.1 linkuse as main transcript	c.1779-202T>C		intron_variant			NM_001374736.1	ENSP00000505098

Frequencies

GnomAD3 genomes

AF:

0.000841

AC:

128

AN:

152236

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000289

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000523

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00156

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000494

AC:

124

AN:

251144

Hom.:

AF XY:

0.000538

AC XY:

AN XY:

135714

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.000145

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.000987

Gnomad OTH exome

AF:

0.000653

GnomAD4 exome

AF:

0.00109

AC:

1587

AN:

1461788

Hom.:

Cov.:

AF XY:

0.00103

AC XY:

748

AN XY:

727190

show subpopulations

Gnomad4 AFR exome

AF:

0.000119

Gnomad4 AMR exome

AF:

0.000157

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000464

Gnomad4 FIN exome

AF:

0.0000749

Gnomad4 NFE exome

AF:

0.00136

Gnomad4 OTH exome

AF:

0.000960

GnomAD4 genome

AF:

0.000840

AC:

128

AN:

152354

Hom.:

Cov.:

AF XY:

0.000752

AC XY:

AN XY:

74506

show subpopulations

Gnomad4 AFR

AF:

0.000289

Gnomad4 AMR

AF:

0.000523

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00156

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000823

Hom.:

Bravo

AF:

0.000691

EpiCase

AF:

0.000982

EpiControl

AF:

0.00107

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Hereditary sensory and autonomic neuropathy type 6;C3809470:Epidermolysis bullosa simplex 3, localized or generalized intermediate, with BP230 deficiency

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 19, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.64

CADD

Benign

DANN

Benign

0.71

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

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