rs10807124

Positions:

• chr6-33436287-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006772.3(SYNGAP1):​c.762+674G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.239 in 151,114 control chromosomes in the GnomAD database, including 5,638 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.24 (5638 hom., cov: 31)
• Consequence: SYNGAP1 NM_006772.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.402

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]

SYNGAP1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.33 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SYNGAP1	NM_006772.3	c.762+674G>A		intron_variant		ENST00000646630.1	NP_006763.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SYNGAP1	ENST00000646630.1	c.762+674G>A		intron_variant			NM_006772.3	ENSP00000496007.1
SYNGAP1	ENST00000644458.1	c.762+674G>A		intron_variant				ENSP00000495541.1
SYNGAP1	ENST00000449372.7	c.762+674G>A		intron_variant		5		ENSP00000416519.4
SYNGAP1	ENST00000418600.7	c.762+674G>A		intron_variant		5		ENSP00000403636.3
SYNGAP1	ENST00000645250.1	c.585+674G>A		intron_variant				ENSP00000494861.1

Frequencies

GnomAD3 genomes AF: 0.239 AC: 36062 AN: 151056 Hom.: 5642 Cov.: 31

Gnomad AFR AF: 0.0496

Gnomad AMI AF: 0.191

Gnomad AMR AF: 0.292

Gnomad ASJ AF: 0.214

Gnomad EAS AF: 0.279

Gnomad SAS AF: 0.343

Gnomad FIN AF: 0.520

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.291

Gnomad OTH AF: 0.195

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.239 AC: 36053 AN: 151114 Hom.: 5638 Cov.: 31 AF XY: 0.251 AC XY: 18485 AN XY: 73772

Gnomad4 AFR AF: 0.0495

Gnomad4 AMR AF: 0.292

Gnomad4 ASJ AF: 0.214

Gnomad4 EAS AF: 0.278

Gnomad4 SAS AF: 0.343

Gnomad4 FIN AF: 0.520

Gnomad4 NFE AF: 0.291

Gnomad4 OTH AF: 0.193

Alfa AF: 0.275 Hom.: 2245

Bravo AF: 0.211

Asia WGS AF: 0.241 AC: 837 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.6
DANN	Benign	0.54

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs10807124; hg19: chr6-33404064;