rs137865390
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Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7
The NM_001723.7(DST):āc.84T>Cā(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 (ā ).
Frequency
Genomes: š 0.00084 ( 0 hom., cov: 33)
Exomes š: 0.0011 ( 0 hom. )
Consequence
DST
NM_001723.7 synonymous
NM_001723.7 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.68
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 -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 | UniProt |
---|---|---|---|---|---|---|---|
DST | NM_001723.7 | c.84T>C | p.Asn28= | synonymous_variant | 1/24 | ENST00000370765.11 | |
DST | NM_001374736.1 | c.1779-202T>C | intron_variant | ENST00000680361.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DST | ENST00000370765.11 | c.84T>C | p.Asn28= | synonymous_variant | 1/24 | 1 | NM_001723.7 | ||
DST | ENST00000680361.1 | c.1779-202T>C | intron_variant | NM_001374736.1 |
Frequencies
GnomAD3 genomes ? AF: 0.000841 AC: 128AN: 152236Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000494 AC: 124AN: 251144Hom.: 0 AF XY: 0.000538 AC XY: 73AN XY: 135714
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GnomAD4 exome AF: 0.00109 AC: 1587AN: 1461788Hom.: 0 Cov.: 32 AF XY: 0.00103 AC XY: 748AN XY: 727190
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GnomAD4 genome ? AF: 0.000840 AC: 128AN: 152354Hom.: 0 Cov.: 33 AF XY: 0.000752 AC XY: 56AN XY: 74506
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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 | Invitae | Jan 19, 2024 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
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DANN
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at