rs147406105
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Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6BP7
The NM_001374736.1(DST):āc.4906T>Cā(p.Leu1636=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000287 in 1,612,924 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: š 0.0018 ( 0 hom., cov: 32)
Exomes š: 0.00013 ( 1 hom. )
Consequence
DST
NM_001374736.1 synonymous
NM_001374736.1 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.120
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]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.74).
BP6
Variant 6-56624553-A-G is Benign according to our data. Variant chr6-56624553-A-G is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 357590.We mark this variant Likely_benign, oryginal submissions are: {Benign=1, Uncertain_significance=1}. Variant chr6-56624553-A-G is described in Lovd as [Likely_benign].
BP7
Synonymous conserved (PhyloP=0.12 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DST | NM_001374736.1 | c.4906T>C | p.Leu1636= | synonymous_variant | 36/104 | ENST00000680361.1 | |
DST | NM_001723.7 | c.3295T>C | p.Leu1099= | synonymous_variant | 22/24 | ENST00000370765.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DST | ENST00000680361.1 | c.4906T>C | p.Leu1636= | synonymous_variant | 36/104 | NM_001374736.1 | |||
DST | ENST00000370765.11 | c.3295T>C | p.Leu1099= | synonymous_variant | 22/24 | 1 | NM_001723.7 |
Frequencies
GnomAD3 genomes AF: 0.00174 AC: 265AN: 152094Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000398 AC: 100AN: 250960Hom.: 1 AF XY: 0.000310 AC XY: 42AN XY: 135642
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GnomAD4 exome AF: 0.000134 AC: 196AN: 1460712Hom.: 1 Cov.: 30 AF XY: 0.000105 AC XY: 76AN XY: 726774
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GnomAD4 genome AF: 0.00175 AC: 267AN: 152212Hom.: 0 Cov.: 32 AF XY: 0.00168 AC XY: 125AN XY: 74430
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:1
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Hereditary sensory and autonomic neuropathy type 6 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Hereditary sensory and autonomic neuropathy type 6;C3809470:Epidermolysis bullosa simplex 3, localized or generalized intermediate, with BP230 deficiency Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at