NM_006772.3:c.3198T>G

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_006772.3(SYNGAP1):​c.3198T>G​(p.Pro1066Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000162 in 1,607,478 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 0.0000066 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000017 ( 0 hom. )

Consequence

SYNGAP1
NM_006772.3 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.0890

Publications

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

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -17 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.59).
BP6
Variant 6-33443750-T-G is Benign according to our data. Variant chr6-33443750-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 416788.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-0.089 with no splicing effect.
BS2
High AC in GnomAdExome4 at 25 AD,Unknown gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SYNGAP1NM_006772.3 linkc.3198T>G p.Pro1066Pro synonymous_variant Exon 15 of 19 ENST00000646630.1 NP_006763.2 Q96PV0-1A0A1U9X8L0

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SYNGAP1ENST00000646630.1 linkc.3198T>G p.Pro1066Pro synonymous_variant Exon 15 of 19 NM_006772.3 ENSP00000496007.1 Q96PV0-1
SYNGAP1ENST00000644458.1 linkc.3198T>G p.Pro1066Pro synonymous_variant Exon 15 of 19 ENSP00000495541.1 A0A2R8Y6T2
SYNGAP1ENST00000449372.7 linkc.3156T>G p.Pro1052Pro synonymous_variant Exon 14 of 18 5 ENSP00000416519.4 B7ZCA0
SYNGAP1ENST00000418600.7 linkc.3198T>G p.Pro1066Pro synonymous_variant Exon 15 of 19 5 ENSP00000403636.3 Q96PV0-2
SYNGAP1ENST00000645250.1 linkc.3021T>G p.Pro1007Pro synonymous_variant Exon 13 of 17 ENSP00000494861.1 A0A2R8YDS2

Frequencies

GnomAD3 genomes
AF:
0.00000660
AC:
1
AN:
151520
Hom.:
0
Cov.:
31
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:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD2 exomes
AF:
0.0000207
AC:
5
AN:
241552
AF XY:
0.0000226
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000583
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000187
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000172
AC:
25
AN:
1455958
Hom.:
0
Cov.:
65
AF XY:
0.0000180
AC XY:
13
AN XY:
723386
show subpopulations
African (AFR)
AF:
0.000120
AC:
4
AN:
33380
American (AMR)
AF:
0.0000449
AC:
2
AN:
44574
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
25962
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39572
South Asian (SAS)
AF:
0.0000232
AC:
2
AN:
86076
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
51902
Middle Eastern (MID)
AF:
0.000348
AC:
2
AN:
5750
European-Non Finnish (NFE)
AF:
0.0000117
AC:
13
AN:
1108566
Other (OTH)
AF:
0.0000332
AC:
2
AN:
60176
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.467
Heterozygous variant carriers
0
2
4
5
7
9
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<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:
0.00000660
AC:
1
AN:
151520
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
73966
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
41172
American (AMR)
AF:
0.00
AC:
0
AN:
15244
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3464
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5162
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4780
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10542
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
312
European-Non Finnish (NFE)
AF:
0.0000147
AC:
1
AN:
67848
Other (OTH)
AF:
0.00
AC:
0
AN:
2084
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
0.00
Hom.:
0
Bravo
AF:
0.0000264
EpiCase
AF:
0.00
EpiControl
AF:
0.000119

ClinVar

Significance: Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

Intellectual disability, autosomal dominant 5 Benign:1
Nov 24, 2024
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

SYNGAP1-related disorder Benign:1
Jun 21, 2019
PreventionGenetics, part of Exact Sciences
Significance:Likely benign
Review Status:no assertion criteria provided
Collection Method:clinical testing

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). -

not provided Benign:1
Jun 01, 2021
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
-0.59
CADD
Benign
3.6
DANN
Benign
0.57
PhyloP100
-0.089
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.9
Mutation Taster
=91/9
polymorphism

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
Details are displayed if max score is > 0.2

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

Publications

Other links and lift over

dbSNP: rs781201249; hg19: chr6-33411527; API