rs411136

Positions:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_006772.3(SYNGAP1):c.1713G>A(p.Ser571Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.404 in 1,606,116 control chromosomes in the GnomAD database, including 134,662 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.36 ( 10569 hom., cov: 31)

Exomes 𝑓: 0.41 ( 124093 hom. )

Consequence

SYNGAP1
NM_006772.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -4.11

Variant links:

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 links:

SYNGAP1-AS1 (HGNC:53831): (SYNGAP1 antisense RNA 1)

SYNGAP1-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 6-33440765-G-A is Benign according to our data. Variant chr6-33440765-G-A is described in ClinVar as [Benign]. Clinvar id is 130524.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-33440765-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-4.11 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.589 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SYNGAP1	NM_006772.3 link	c.1713G>A	p.Ser571Ser	synonymous_variant	11/19	ENST00000646630.1	NP_006763.2	Q96PV0-1A0A1U9X8L0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SYNGAP1	ENST00000646630.1 link	c.1713G>A	p.Ser571Ser	synonymous_variant	11/19		NM_006772.3	ENSP00000496007.1	Q96PV0-1
SYNGAP1	ENST00000644458.1 link	c.1713G>A	p.Ser571Ser	synonymous_variant	11/19			ENSP00000495541.1	A0A2R8Y6T2
SYNGAP1	ENST00000449372.7 link	c.1713G>A	p.Ser571Ser	synonymous_variant	11/18	5		ENSP00000416519.4	B7ZCA0
SYNGAP1	ENST00000418600.7 link	c.1713G>A	p.Ser571Ser	synonymous_variant	11/19	5		ENSP00000403636.3	Q96PV0-2
SYNGAP1	ENST00000645250.1 link	c.1536G>A	p.Ser512Ser	synonymous_variant	9/17			ENSP00000494861.1	A0A2R8YDS2

Frequencies

GnomAD3 genomes

AF:

0.364

AC:

55343

AN:

151906

Hom.:

10559

Cov.:

show subpopulations

Gnomad AFR

AF:

0.278

Gnomad AMI

AF:

0.471

Gnomad AMR

AF:

0.385

Gnomad ASJ

AF:

0.425

Gnomad EAS

AF:

0.606

Gnomad SAS

AF:

0.505

Gnomad FIN

AF:

0.255

Gnomad MID

AF:

0.443

Gnomad NFE

AF:

0.395

Gnomad OTH

AF:

0.394

GnomAD3 exomes

AF:

0.402

AC:

95212

AN:

236684

Hom.:

19841

AF XY:

0.408

AC XY:

52317

AN XY:

128360

show subpopulations

Gnomad AFR exome

AF:

0.276

Gnomad AMR exome

AF:

0.363

Gnomad ASJ exome

AF:

0.437

Gnomad EAS exome

AF:

0.609

Gnomad SAS exome

AF:

0.501

Gnomad FIN exome

AF:

0.274

Gnomad NFE exome

AF:

0.392

Gnomad OTH exome

AF:

0.405

GnomAD4 exome

AF:

0.408

AC:

593907

AN:

1454092

Hom.:

124093

Cov.:

AF XY:

0.411

AC XY:

297327

AN XY:

722766

show subpopulations

Gnomad4 AFR exome

AF:

0.271

Gnomad4 AMR exome

AF:

0.367

Gnomad4 ASJ exome

AF:

0.436

Gnomad4 EAS exome

AF:

0.638

Gnomad4 SAS exome

AF:

0.499

Gnomad4 FIN exome

AF:

0.278

Gnomad4 NFE exome

AF:

0.404

Gnomad4 OTH exome

AF:

0.408

GnomAD4 genome

AF:

0.364

AC:

55368

AN:

152024

Hom.:

10569

Cov.:

AF XY:

0.361

AC XY:

26862

AN XY:

74336

show subpopulations

Gnomad4 AFR

AF:

0.278

Gnomad4 AMR

AF:

0.385

Gnomad4 ASJ

AF:

0.425

Gnomad4 EAS

AF:

0.607

Gnomad4 SAS

AF:

0.506

Gnomad4 FIN

AF:

0.255

Gnomad4 NFE

AF:

0.395

Gnomad4 OTH

AF:

0.397

Alfa

AF:

0.381

Hom.:

12038

Bravo

AF:

0.366

Asia WGS

AF:

0.566

AC:

1966

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Likely benign, no assertion criteria provided	clinical testing	Genetic Services Laboratory, University of Chicago	-	Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 28, 2016	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, criteria provided, single submitter	clinical testing	Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan	Jul 15, 2024	This variant is classified as Benign based on local population frequency. This variant was detected in 62% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 58. Only high quality variants are reported. -

Inborn genetic diseases

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 08, 2016

This alteration is classified as 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

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 04, 2025

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

1.7

DANN

Benign

0.93

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over