rs779377737

Variant names:

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2

The NM_006772.3(SYNGAP1):c.3369C>T(p.Gly1123Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000302 in 959,724 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 Likely benign (★★).

Frequency

Genomes: 𝑓 0.0000071 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000034 ( 0 hom. )

Consequence

SYNGAP1
NM_006772.3 synonymous

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.545

Publications

1 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 -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.36).

BP6

Variant 6-33443921-C-T is Benign according to our data. Variant chr6-33443921-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 537015.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.545 with no splicing effect.

BS2

High AC in GnomAdExome4 at 28 AD,Unknown gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYNGAP1	NM_006772.3 link	c.3369C>T	p.Gly1123Gly	synonymous_variant	Exon 15 of 19	ENST00000646630.1	NP_006763.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
SYNGAP1	ENST00000646630.1 link	c.3369C>T	p.Gly1123Gly	synonymous_variant	Exon 15 of 19		NM_006772.3	ENSP00000496007.1
SYNGAP1	ENST00000644458.1 link	c.3369C>T	p.Gly1123Gly	synonymous_variant	Exon 15 of 19			ENSP00000495541.1
SYNGAP1	ENST00000449372.7 link	c.3327C>T	p.Gly1109Gly	synonymous_variant	Exon 14 of 18	5		ENSP00000416519.4
SYNGAP1	ENST00000418600.7 link	c.3369C>T	p.Gly1123Gly	synonymous_variant	Exon 15 of 19	5		ENSP00000403636.3
SYNGAP1	ENST00000645250.1 link	c.3192C>T	p.Gly1064Gly	synonymous_variant	Exon 13 of 17			ENSP00000494861.1

Frequencies

GnomAD3 genomes

AF:

0.00000715

AC:

AN:

139958

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000156

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000217

AC:

AN:

138540

AF XY:

0.0000268

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000772

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000311

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000342

AC:

AN:

819766

Hom.:

Cov.:

AF XY:

0.0000298

AC XY:

AN XY:

403316

show subpopulations

African (AFR)

AF:

0.0000544

AC:

AN:

18370

American (AMR)

AF:

0.00

AC:

AN:

19542

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

9428

East Asian (EAS)

AF:

0.0000555

AC:

AN:

18016

South Asian (SAS)

AF:

0.0000188

AC:

AN:

53212

European-Finnish (FIN)

AF:

0.00

AC:

AN:

27632

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2982

European-Non Finnish (NFE)

AF:

0.0000391

AC:

AN:

640138

Other (OTH)

AF:

0.00

AC:

AN:

30446

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.457

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.00000715

AC:

AN:

139958

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

68238

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

38198

American (AMR)

AF:

0.00

AC:

AN:

14174

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3334

East Asian (EAS)

AF:

0.00

AC:

AN:

4246

South Asian (SAS)

AF:

0.00

AC:

AN:

3804

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8908

Middle Eastern (MID)

AF:

0.00

AC:

AN:

298

European-Non Finnish (NFE)

AF:

0.0000156

AC:

AN:

64216

Other (OTH)

AF:

0.00

AC:

AN:

1964

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

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:

0.00

Hom.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Intellectual disability, autosomal dominant 5

Benign:1

Aug 18, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Jun 01, 2020

CeGaT Center for Human Genetics Tuebingen

Significance:Likely 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

-0.36

CADD

Benign

(source)

DANN

Benign

0.62

PhyloP100

0.55

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.11

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