Variant chr6-33451846-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_StrongBP6_ModerateBP7

The NM_006772.3(SYNGAP1):c.3972A>C(p.Pro1324=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.11 ( 0 hom., cov: 0)

Exomes 𝑓: 0.27 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SYNGAP1
NM_006772.3 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.189

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 -7 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.7).

BP6

Variant 6-33451846-A-C is Benign according to our data. Variant chr6-33451846-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 537023.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.189 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SYNGAP1	NM_006772.3 linkuse as main transcript	c.3972A>C	p.Pro1324=	synonymous_variant	19/19	ENST00000646630.1	NP_006763.2
SYNGAP1-AS1	NR_174954.1 linkuse as main transcript	n.136+2424T>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SYNGAP1	ENST00000646630.1 linkuse as main transcript	c.3972A>C	p.Pro1324=	synonymous_variant	19/19		NM_006772.3	ENSP00000496007	P1	Q96PV0-1
SYNGAP1-AS1	ENST00000630418.1 linkuse as main transcript	n.184+2424T>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

2636

AN:

23070

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.111

Gnomad AMI

AF:

0.0946

Gnomad AMR

AF:

0.0713

Gnomad ASJ

AF:

0.144

Gnomad EAS

AF:

0.0378

Gnomad SAS

AF:

0.0913

Gnomad FIN

AF:

0.0996

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.135

Gnomad OTH

AF:

0.129

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.273

AC:

72337

AN:

264912

Hom.:

Cov.:

AF XY:

0.263

AC XY:

35451

AN XY:

134898

show subpopulations

Gnomad4 AFR exome

AF:

0.243

Gnomad4 AMR exome

AF:

0.145

Gnomad4 ASJ exome

AF:

0.144

Gnomad4 EAS exome

AF:

0.111

Gnomad4 SAS exome

AF:

0.252

Gnomad4 FIN exome

AF:

0.100

Gnomad4 NFE exome

AF:

0.303

Gnomad4 OTH exome

AF:

0.251

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.114

AC:

2635

AN:

23098

Hom.:

Cov.:

AF XY:

0.109

AC XY:

1245

AN XY:

11444

show subpopulations

Gnomad4 AFR

AF:

0.111

Gnomad4 AMR

AF:

0.0713

Gnomad4 ASJ

AF:

0.144

Gnomad4 EAS

AF:

0.0381

Gnomad4 SAS

AF:

0.0893

Gnomad4 FIN

AF:

0.0996

Gnomad4 NFE

AF:

0.135

Gnomad4 OTH

AF:

0.129

Alfa

AF:

0.00119

Hom.:

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

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 17, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.70

CADD

Benign

5.8

DANN

Benign

0.57

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