rs764031180

chr6-33451843-A-C

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_006772.3(SYNGAP1):c.3969A>C(p.Pro1323=) 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 0.12 (0 hom., cov: 0)
  • Exomes 𝑓: 0.33 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SYNGAP1 NM_006772.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.396

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)

ACMG classification

Verdict is Benign. Variant got -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BP6: Variant 6-33451843-A-C is Benign according to our data. Variant chr6-33451843-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 537011.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.396 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SYNGAP1	NM_006772.3	c.3969A>C	p.Pro1323=	synonymous_variant	19/19	ENST00000646630.1
SYNGAP1-AS1	NR_174954.1	n.136+2427T>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SYNGAP1	ENST00000646630.1	c.3969A>C	p.Pro1323=	synonymous_variant	19/19		NM_006772.3	P1
SYNGAP1-AS1	ENST00000630418.1	n.184+2427T>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.00 AC: 2816 AN: 24056 Hom.: 0 Cov.: 0 FAILED QC

Gnomad AFR AF: 0.116

Gnomad AMI AF: 0.105

Gnomad AMR AF: 0.0784

Gnomad ASJ AF: 0.141

Gnomad EAS AF: 0.0441

Gnomad SAS AF: 0.0929

Gnomad FIN AF: 0.0964

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.136

Gnomad OTH AF: 0.115

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.331 AC: 88747 AN: 267954 Hom.: 0 Cov.: 21 AF XY: 0.323 AC XY: 42874 AN XY: 132836

Gnomad4 AFR exome AF: 0.310

Gnomad4 AMR exome AF: 0.211

Gnomad4 ASJ exome AF: 0.215

Gnomad4 EAS exome AF: 0.158

Gnomad4 SAS exome AF: 0.310

Gnomad4 FIN exome AF: 0.141

Gnomad4 NFE exome AF: 0.355

Gnomad4 OTH exome AF: 0.311

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.117 AC: 2817 AN: 24088 Hom.: 0 Cov.: 0 AF XY: 0.114 AC XY: 1342 AN XY: 11814

Gnomad4 AFR AF: 0.116

Gnomad4 AMR AF: 0.0786

Gnomad4 ASJ AF: 0.141

Gnomad4 EAS AF: 0.0444

Gnomad4 SAS AF: 0.0924

Gnomad4 FIN AF: 0.0964

Gnomad4 NFE AF: 0.136

Gnomad4 OTH AF: 0.115

Alfa AF: 0.00173 Hom.: 0

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Intellectual disability, autosomal dominant 5 Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jan 17, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
Cadd	Benign	6.6
Dann	Benign	0.59

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

Other links and lift over

dbSNP: rs764031180; hg19: chr6-33419620; COSMIC: COSV53382165; COSMIC: COSV53382165;