rs1478769596
Positions:
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_ModerateBP6BP7BS2
The NM_006772.3(SYNGAP1):c.3363C>T(p.Ser1121=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000185 in 921,188 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: not found (cov: 31)
Exomes 𝑓: 0.000018 ( 0 hom. )
Consequence
SYNGAP1
NM_006772.3 synonymous
NM_006772.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.887
Genes affected
SYNGAP1 (HGNC:11497): (synaptic Ras GTPase activating protein 1) This gene encodes a Ras GTPase activating protein that is a member of the N-methyl-D-aspartate receptor complex. The N-terminal domain of the protein contains a Ras-GAP domain, a pleckstrin homology domain, and a C2 domain that may be involved in binding of calcium and phospholipids. The C-terminal domain consists of a ten histidine repeat region, serine and tyrosine phosphorylation sites, and a T/SXV motif required for postsynaptic scaffold protein interaction. The encoded protein negatively regulates Ras, Rap and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor trafficking to the postsynaptic membrane to regulate synaptic plasticity and neuronal homeostasis. Allelic variants of this gene are associated with intellectual disability and autism spectrum disorder. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2016]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -8 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.38).
BP6
Variant 6-33443915-C-T is Benign according to our data. Variant chr6-33443915-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 436919.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}.
BP7
Synonymous conserved (PhyloP=0.887 with no splicing effect.
BS2
High AC in GnomAdExome4 at 17 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SYNGAP1 | NM_006772.3 | c.3363C>T | p.Ser1121= | synonymous_variant | 15/19 | ENST00000646630.1 | |
SYNGAP1-AS1 | NR_174954.1 | n.329+2691G>A | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SYNGAP1 | ENST00000646630.1 | c.3363C>T | p.Ser1121= | synonymous_variant | 15/19 | NM_006772.3 | P1 | ||
SYNGAP1-AS1 | ENST00000630418.1 | n.377+2691G>A | intron_variant, non_coding_transcript_variant | 5 |
Frequencies
GnomAD3 genomes Cov.: 31
GnomAD3 genomes
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31
GnomAD4 exome AF: 0.0000185 AC: 17AN: 921188Hom.: 0 Cov.: 44 AF XY: 0.0000266 AC XY: 12AN XY: 451930
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12
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451930
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GnomAD4 genome Cov.: 31
GnomAD4 genome
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31
Bravo
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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
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Aug 22, 2016 | - - |
Intellectual disability, autosomal dominant 5 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Nov 10, 2023 | - - |
Computational scores
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Name
Calibrated prediction
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Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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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