rs543767625
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Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6BP7
The NM_001723.7(DST):āc.3957A>Cā(p.Ala1319=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000459 in 1,613,740 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 Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: š 0.000085 ( 0 hom., cov: 32)
Exomes š: 0.000042 ( 0 hom. )
Consequence
DST
NM_001723.7 synonymous
NM_001723.7 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.29
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=-0.48).
BP6
?
Variant 6-56620077-T-G is Benign according to our data. Variant chr6-56620077-T-G is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 357582.We mark this variant Likely_benign, oryginal submissions are: {Benign=1, Uncertain_significance=1}.
BP7
?
Synonymous conserved (PhyloP=-1.29 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DST | NM_001723.7 | c.3957A>C | p.Ala1319= | synonymous_variant | 23/24 | ENST00000370765.11 | |
DST | NM_001374736.1 | c.4929+4453A>C | intron_variant | ENST00000680361.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DST | ENST00000370765.11 | c.3957A>C | p.Ala1319= | synonymous_variant | 23/24 | 1 | NM_001723.7 | ||
DST | ENST00000680361.1 | c.4929+4453A>C | intron_variant | NM_001374736.1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000854 AC: 13AN: 152212Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000231 AC: 58AN: 250824Hom.: 0 AF XY: 0.000177 AC XY: 24AN XY: 135602
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GnomAD4 exome AF: 0.0000417 AC: 61AN: 1461410Hom.: 0 Cov.: 34 AF XY: 0.0000330 AC XY: 24AN XY: 727046
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GnomAD4 genome ? AF: 0.0000853 AC: 13AN: 152330Hom.: 0 Cov.: 32 AF XY: 0.0000806 AC XY: 6AN XY: 74484
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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 | Sep 23, 2021 | - - |
Computational scores
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Name
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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