rs387907363
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Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_004782.4(SNAP29):c.487dup(p.Ser163LysfsTer6) variant causes a frameshift change. The variant allele was found at a frequency of 0.0000161 in 1,612,806 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000016 ( 0 hom. )
Consequence
SNAP29
NM_004782.4 frameshift
NM_004782.4 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 6.47
Genes affected
SNAP29 (HGNC:11133): (synaptosome associated protein 29) This gene, a member of the SNAP25 gene family, encodes a protein involved in multiple membrane trafficking steps. Two other members of this gene family, SNAP23 and SNAP25, encode proteins that bind a syntaxin protein and mediate synaptic vesicle membrane docking and fusion to the plasma membrane. The protein encoded by this gene binds tightly to multiple syntaxins and is localized to intracellular membrane structures rather than to the plasma membrane. While the protein is mostly membrane-bound, a significant fraction of it is found free in the cytoplasm. Use of multiple polyadenylation sites has been noted for this gene. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 18 ACMG points.
PVS1
?
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
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Very rare variant in population databases, with high coverage;
PP5
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Variant 22-20881100-C-CA is Pathogenic according to our data. Variant chr22-20881100-C-CA is described in ClinVar as [Pathogenic]. Clinvar id is 50295.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SNAP29 | NM_004782.4 | c.487dup | p.Ser163LysfsTer6 | frameshift_variant | 3/5 | ENST00000215730.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SNAP29 | ENST00000215730.12 | c.487dup | p.Ser163LysfsTer6 | frameshift_variant | 3/5 | 1 | NM_004782.4 | P1 | |
SNAP29 | ENST00000439214.1 | c.208dup | p.Ser70LysfsTer6 | frameshift_variant | 3/5 | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152160Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000318 AC: 8AN: 251394Hom.: 0 AF XY: 0.0000442 AC XY: 6AN XY: 135870
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GnomAD4 exome AF: 0.0000164 AC: 24AN: 1460646Hom.: 0 Cov.: 29 AF XY: 0.0000234 AC XY: 17AN XY: 726736
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ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Pathogenic:3
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Jan 04, 2024 | This sequence change creates a premature translational stop signal (p.Ser163Lysfs*6) in the SNAP29 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SNAP29 are known to be pathogenic (PMID: 15968592, 21073448). This variant is present in population databases (rs768735498, gnomAD 0.03%). This premature translational stop signal has been observed in individual(s) with cerebral dysgenesis, neuropathy, ichthyosis, and palmoplantar keratoderma syndrome (PMID: 21073448). This variant is also known as c.486insA. ClinVar contains an entry for this variant (Variation ID: 50295). For these reasons, this variant has been classified as Pathogenic. - |
Pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Sep 15, 2023 | Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 28388629, 21073448, 25958742, 33977139, 35568357, 31069529) - |
Pathogenic, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Oct 25, 2017 | - - |
CEDNIK syndrome Pathogenic:2
Pathogenic, criteria provided, single submitter | research | Department of Medical Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences | - | - - |
Pathogenic, no assertion criteria provided | literature only | OMIM | Mar 01, 2011 | - - |
Computational scores
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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