rs773687127

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_006772.3(SYNGAP1):​c.2628G>A​(p.Ser876Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000868 in 1,613,546 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 0.000026 ( 0 hom., cov: 31)
Exomes 𝑓: 0.0000068 ( 0 hom. )

Consequence

SYNGAP1
NM_006772.3 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.89

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-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 -11 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.64).
BP6
Variant 6-33443180-G-A is Benign according to our data. Variant chr6-33443180-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 469151.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=-1.89 with no splicing effect.
BS2
High AC in GnomAdExome4 at 10 AD,Unknown gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SYNGAP1NM_006772.3 linkc.2628G>A p.Ser876Ser 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.2628G>A p.Ser876Ser synonymous_variant Exon 15 of 19 NM_006772.3 ENSP00000496007.1 Q96PV0-1
SYNGAP1ENST00000644458.1 linkc.2628G>A p.Ser876Ser synonymous_variant Exon 15 of 19 ENSP00000495541.1 A0A2R8Y6T2
SYNGAP1ENST00000449372.7 linkc.2586G>A p.Ser862Ser synonymous_variant Exon 14 of 18 5 ENSP00000416519.4 B7ZCA0
SYNGAP1ENST00000418600.7 linkc.2628G>A p.Ser876Ser synonymous_variant Exon 15 of 19 5 ENSP00000403636.3 Q96PV0-2
SYNGAP1ENST00000645250.1 linkc.2451G>A p.Ser817Ser synonymous_variant Exon 13 of 17 ENSP00000494861.1 A0A2R8YDS2

Frequencies

GnomAD3 genomes
AF:
0.0000263
AC:
4
AN:
152202
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0000724
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000654
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD2 exomes
AF:
0.00000801
AC:
2
AN:
249638
AF XY:
0.00000740
show subpopulations
Gnomad AFR exome
AF:
0.0000618
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000684
AC:
10
AN:
1461344
Hom.:
0
Cov.:
32
AF XY:
0.00000688
AC XY:
5
AN XY:
727012
show subpopulations
African (AFR)
AF:
0.000119
AC:
4
AN:
33480
American (AMR)
AF:
0.0000447
AC:
2
AN:
44716
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26124
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39700
South Asian (SAS)
AF:
0.0000116
AC:
1
AN:
86254
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
52970
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
0.00000180
AC:
2
AN:
1111948
Other (OTH)
AF:
0.0000166
AC:
1
AN:
60384
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.465
Heterozygous variant carriers
0
1
2
4
5
6
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:
0.0000263
AC:
4
AN:
152202
Hom.:
0
Cov.:
31
AF XY:
0.0000404
AC XY:
3
AN XY:
74346
show subpopulations
African (AFR)
AF:
0.0000724
AC:
3
AN:
41452
American (AMR)
AF:
0.0000654
AC:
1
AN:
15294
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3472
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5178
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4830
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10624
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
68032
Other (OTH)
AF:
0.00
AC:
0
AN:
2094
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.438
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome 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
Alfa
AF:
0.0000331
Hom.:
0
Bravo
AF:
0.0000189
Asia WGS
AF:
0.000289
AC:
1
AN:
3478

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Intellectual disability, autosomal dominant 5 Benign:1
Oct 16, 2024
Labcorp Genetics (formerly Invitae), Labcorp
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
-0.64
CADD
Benign
2.1
DANN
Benign
0.88
PhyloP100
-1.9
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

Other links and lift over

dbSNP: rs773687127; hg19: chr6-33410957; COSMIC: COSV53384179; COSMIC: COSV53384179; API