rs1135401768
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_001145358.2(SIN3A):c.3118_3119del(p.Gln1040GlufsTer15) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 31)
Exomes 𝑓: 6.8e-7 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
SIN3A
NM_001145358.2 frameshift
NM_001145358.2 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 9.98
Genes affected
SIN3A (HGNC:19353): (SIN3 transcription regulator family member A) The protein encoded by this gene is a transcriptional regulatory protein. It contains paired amphipathic helix (PAH) domains, which are important for protein-protein interactions and may mediate repression by the Mad-Max complex. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 12 ACMG points.
PVS1
?
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 15-75384339-CTG-C is Pathogenic according to our data. Variant chr15-75384339-CTG-C is described in ClinVar as [Pathogenic]. Clinvar id is 431101.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr15-75384339-CTG-C is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SIN3A | NM_001145358.2 | c.3118_3119del | p.Gln1040GlufsTer15 | frameshift_variant | 17/21 | ENST00000394947.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SIN3A | ENST00000394947.8 | c.3118_3119del | p.Gln1040GlufsTer15 | frameshift_variant | 17/21 | 1 | NM_001145358.2 | P4 |
Frequencies
GnomAD3 genomes ? Cov.: 31
GnomAD3 genomes
?
Cov.:
31
GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 6.84e-7 AC: 1AN: 1461342Hom.: 0 AF XY: 0.00000138 AC XY: 1AN XY: 727008
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
AC:
1
AN:
1461342
Hom.:
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1
AN XY:
727008
Gnomad4 AFR exome
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GnomAD4 genome ? Cov.: 31
GnomAD4 genome
?
Cov.:
31
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
SIN3A-related intellectual disability syndrome due to a point mutation Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Institute of Human Genetics, FAU Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg | Aug 01, 2017 | LOF variant in a patient with mild ID, behavioral anomalies (ADHD), obesity, height at 97th centile. - |
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