rs758101067
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 4P and 5B. PM1PP2PP3BP6BS2
The NM_006772.3(SYNGAP1):c.1723C>T(p.Arg575Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000143 in 1,609,098 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. R575H) has been classified as Likely benign.
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.1723C>T | p.Arg575Cys | missense_variant | 11/19 | ENST00000646630.1 | |
SYNGAP1-AS1 | NR_174954.1 | n.330-3294G>A | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SYNGAP1 | ENST00000646630.1 | c.1723C>T | p.Arg575Cys | missense_variant | 11/19 | NM_006772.3 | P1 | ||
SYNGAP1-AS1 | ENST00000630418.1 | n.378-3294G>A | intron_variant, non_coding_transcript_variant | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152210Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.0000125 AC: 3AN: 239748Hom.: 0 AF XY: 0.0000154 AC XY: 2AN XY: 130188
GnomAD4 exome AF: 0.0000151 AC: 22AN: 1456888Hom.: 0 Cov.: 39 AF XY: 0.0000138 AC XY: 10AN XY: 724444
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152210Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 74352
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 13, 2017 | The p.R575C variant (also known as c.1723C>T), located in coding exon 11 of the SYNGAP1 gene, results from a C to T substitution at nucleotide position 1723. The arginine at codon 575 is replaced by cysteine, an amino acid with highly dissimilar properties. This variant did not co-segregate with disease in one individual tested in our laboratory. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Intellectual disability, autosomal dominant 5 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Sep 06, 2023 | - - |
SYNGAP1-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Nov 27, 2023 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at