rs77934848

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_006772.3(SYNGAP1):c.1803G>A(p.Ala601Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00166 in 1,614,242 control chromosomes in the GnomAD database, including 55 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. A601A) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0019 ( 4 hom., cov: 31)

Exomes 𝑓: 0.0016 ( 51 hom. )

Consequence

SYNGAP1
NM_006772.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.719

Publications

3 publications found

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 was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.5).

BP6

Variant 6-33440855-G-A is Benign according to our data. Variant chr6-33440855-G-A is described in ClinVar as Benign. ClinVar VariationId is 416776.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.719 with no splicing effect.

BS1

Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.00189 (288/152348) while in subpopulation EAS AF = 0.0384 (199/5188). AF 95% confidence interval is 0.034. There are 4 homozygotes in GnomAd4. There are 144 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.

BS2

High AC in GnomAd4 at 288 AD,Unknown gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYNGAP1	NM_006772.3 link	c.1803G>A	p.Ala601Ala	synonymous_variant	Exon 11 of 19	ENST00000646630.1	NP_006763.2	Q96PV0-1A0A1U9X8L0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SYNGAP1	ENST00000646630.1 link	c.1803G>A	p.Ala601Ala	synonymous_variant	Exon 11 of 19		NM_006772.3	ENSP00000496007.1	Q96PV0-1
SYNGAP1	ENST00000644458.1 link	c.1803G>A	p.Ala601Ala	synonymous_variant	Exon 11 of 19			ENSP00000495541.1	A0A2R8Y6T2
SYNGAP1	ENST00000449372.7 link	c.1803G>A	p.Ala601Ala	synonymous_variant	Exon 11 of 18	5		ENSP00000416519.4	B7ZCA0
SYNGAP1	ENST00000418600.7 link	c.1803G>A	p.Ala601Ala	synonymous_variant	Exon 11 of 19	5		ENSP00000403636.3	Q96PV0-2
SYNGAP1	ENST00000645250.1 link	c.1626G>A	p.Ala542Ala	synonymous_variant	Exon 9 of 17			ENSP00000494861.1	A0A2R8YDS2

Frequencies

GnomAD3 genomes

AF:

0.00190

AC:

289

AN:

152230

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000723

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00170

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0385

Gnomad SAS

AF:

0.00352

Gnomad FIN

AF:

0.00226

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000176

Gnomad OTH

AF:

0.00335

GnomAD2 exomes

AF:

0.00348

AC:

876

AN:

251486

AF XY:

0.00319

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0399

Gnomad FIN exome

AF:

0.00333

Gnomad NFE exome

AF:

0.000237

Gnomad OTH exome

AF:

0.00244

GnomAD4 exome

AF:

0.00164

AC:

2399

AN:

1461894

Hom.:

Cov.:

AF XY:

0.00157

AC XY:

1143

AN XY:

727248

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.0000224

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.0453

AC:

1797

AN:

39700

South Asian (SAS)

AF:

0.000893

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00313

AC:

167

AN:

53420

Middle Eastern (MID)

AF:

0.000520

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000155

AC:

172

AN:

1112012

Other (OTH)

AF:

0.00301

AC:

182

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

192

384

577

769

961

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

108

144

180

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00189

AC:

288

AN:

152348

Hom.:

Cov.:

AF XY:

0.00193

AC XY:

144

AN XY:

74502

show subpopulations

African (AFR)

AF:

0.0000721

AC:

AN:

41590

American (AMR)

AF:

0.00170

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.0384

AC:

199

AN:

5188

South Asian (SAS)

AF:

0.00352

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00226

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000176

AC:

AN:

68024

Other (OTH)

AF:

0.00331

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000538

Hom.:

Bravo

AF:

0.00161

Asia WGS

AF:

0.0170

AC:

AN:

3478

EpiCase

AF:

0.000164

EpiControl

AF:

0.000178

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

May 18, 2021

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Inborn genetic diseases

Benign:1

Mar 24, 2016

Ambry Genetics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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

Jan 28, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

SYNGAP1-related disorder

Benign:1

Sep 19, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided

Benign:1

Apr 06, 2020

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.50

CADD

Benign

(source)

DANN

Benign

0.92

PhyloP100

0.72

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over