chr6-33420292-C-A
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Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_ModerateBP6_ModerateBP7
The NM_006772.3(SYNGAP1):c.28C>A(p.Arg10=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000013 in 1,540,834 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 (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 28)
Exomes 𝑓: 7.2e-7 ( 0 hom. )
Consequence
SYNGAP1
NM_006772.3 synonymous
NM_006772.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.91
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 Likely_benign. Variant got -3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.44).
BP6
Variant 6-33420292-C-A is Benign according to our data. Variant chr6-33420292-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 1008683.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=1.91 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SYNGAP1 | NM_006772.3 | c.28C>A | p.Arg10= | synonymous_variant | 1/19 | ENST00000646630.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SYNGAP1 | ENST00000646630.1 | c.28C>A | p.Arg10= | synonymous_variant | 1/19 | NM_006772.3 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00000660 AC: 1AN: 151534Hom.: 0 Cov.: 28
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GnomAD4 exome AF: 7.20e-7 AC: 1AN: 1389300Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 685024
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GnomAD4 genome AF: 0.00000660 AC: 1AN: 151534Hom.: 0 Cov.: 28 AF XY: 0.0000135 AC XY: 1AN XY: 74008
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Intellectual disability, autosomal dominant 5 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Oct 03, 2023 | - - |
Computational scores
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CADD
Benign
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Benign
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Find out detailed SpliceAI scores and Pangolin per-transcript scores at