rs375587730
Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6BP7BS2
The NM_006772.3(SYNGAP1):c.2583G>A(p.Ser861=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000347 in 1,614,126 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). Synonymous variant affecting the same amino acid position (i.e. S861S) has been classified as Likely benign.
Frequency
Consequence
NM_006772.3 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -10 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SYNGAP1 | NM_006772.3 | c.2583G>A | p.Ser861= | synonymous_variant | 15/19 | ENST00000646630.1 | |
SYNGAP1-AS1 | NR_174954.1 | n.329+3471C>T | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SYNGAP1 | ENST00000646630.1 | c.2583G>A | p.Ser861= | synonymous_variant | 15/19 | NM_006772.3 | P1 | ||
SYNGAP1-AS1 | ENST00000630418.1 | n.377+3471C>T | intron_variant, non_coding_transcript_variant | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000723 AC: 11AN: 152190Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.0000559 AC: 14AN: 250472Hom.: 0 AF XY: 0.0000591 AC XY: 8AN XY: 135436
GnomAD4 exome AF: 0.0000308 AC: 45AN: 1461818Hom.: 0 Cov.: 32 AF XY: 0.0000358 AC XY: 26AN XY: 727214
GnomAD4 genome ? AF: 0.0000722 AC: 11AN: 152308Hom.: 0 Cov.: 31 AF XY: 0.0000537 AC XY: 4AN XY: 74472
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Mar 23, 2015 | - - |
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 10, 2017 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Intellectual disability, autosomal dominant 5 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Sep 10, 2023 | - - |
SYNGAP1-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jul 15, 2019 | 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