rs199694815
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 3P and 7B. PM2PP2BP4_ModerateBP6BS2
The NM_006772.3(SYNGAP1):c.3902C>A(p.Pro1301His) variant causes a missense change. The variant allele was found at a frequency of 0.00000342 in 1,461,430 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). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P1301R) 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 -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SYNGAP1 | NM_006772.3 | c.3902C>A | p.Pro1301His | missense_variant | 19/19 | ENST00000646630.1 | |
SYNGAP1-AS1 | NR_174954.1 | n.136+2494G>T | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SYNGAP1 | ENST00000646630.1 | c.3902C>A | p.Pro1301His | missense_variant | 19/19 | NM_006772.3 | P1 | ||
SYNGAP1-AS1 | ENST00000630418.1 | n.184+2494G>T | intron_variant, non_coding_transcript_variant | 5 |
Frequencies
GnomAD3 genomes ? Cov.: 31
GnomAD4 exome AF: 0.00000342 AC: 5AN: 1461430Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3AN XY: 726978
GnomAD4 genome ? Cov.: 31
ClinVar
Submissions by phenotype
Intellectual disability, autosomal dominant 5 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Apr 01, 2022 | This sequence change replaces proline, which is neutral and non-polar, with histidine, which is basic and polar, at codon 1301 of the SYNGAP1 protein (p.Pro1301His). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with SYNGAP1-related conditions. ClinVar contains an entry for this variant (Variation ID: 212356). 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. 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. - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Mar 04, 2015 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at