chr6-33420293-G-A
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 1P and 2B. PP2BP4_Moderate
The NM_006772.3(SYNGAP1):c.29G>A(p.Arg10Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000144 in 1,390,032 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 Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R10P) has been classified as Uncertain significance.
Frequency
Consequence
NM_006772.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SYNGAP1 | NM_006772.3 | c.29G>A | p.Arg10Gln | missense_variant | 1/19 | ENST00000646630.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SYNGAP1 | ENST00000646630.1 | c.29G>A | p.Arg10Gln | missense_variant | 1/19 | NM_006772.3 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 28
GnomAD4 exome AF: 0.0000144 AC: 20AN: 1390032Hom.: 0 Cov.: 31 AF XY: 0.0000146 AC XY: 10AN XY: 685388
GnomAD4 genome ? Cov.: 28
ClinVar
Submissions by phenotype
Intellectual disability, autosomal dominant 5 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jun 21, 2023 | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt SYNGAP1 protein function. This variant has not been reported in the literature in individuals affected with SYNGAP1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 10 of the SYNGAP1 protein (p.Arg10Gln). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at