Variant 22-39381817-C-CCAA details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 1P and 10B. PM4_SupportingBP6_ModerateBA1

The NM_004711.5(SYNGR1):c.607_608insACA(p.Pro202_Thr203insAsn) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.713 in 1,612,432 control chromosomes in the GnomAD database, including 415,053 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.76 ( 44627 hom., cov: 0)

Exomes 𝑓: 0.71 ( 370426 hom. )

Consequence

SYNGR1
NM_004711.5 disruptive_inframe_insertion

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.13

Variant links:

Genes affected

SYNGR1 (HGNC:11498): (synaptogyrin 1) This gene encodes an integral membrane protein associated with presynaptic vesicles in neuronal cells. The exact function of this protein is unclear, but studies of a similar murine protein suggest that it functions in synaptic plasticity without being required for synaptic transmission. The gene product belongs to the synaptogyrin gene family. Three alternatively spliced variants encoding three different isoforms have been identified. [provided by RefSeq, Jul 2008]

SYNGR1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

PM4

Nonframeshift variant in NON repetitive region in NM_004711.5. Strenght limited to Supporting due to length of the change: 1aa.

BP6

Variant 22-39381817-C-CCAA is Benign according to our data. Variant chr22-39381817-C-CCAA is described in ClinVar as [Benign]. Clinvar id is 979149.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.975 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYNGR1	NM_004711.5 link	c.607_608insACA	p.Pro202_Thr203insAsn	disruptive_inframe_insertion	Exon 4 of 4	ENST00000328933.10	NP_004702.2	O43759-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYNGR1	ENST00000328933.10 link	c.607_608insACA	p.Pro202_Thr203insAsn	disruptive_inframe_insertion	Exon 4 of 4	1	NM_004711.5	ENSP00000332287.5		O43759-1

Frequencies

GnomAD3 genomes

AF:

0.759

AC:

115118

AN:

151640

Hom.:

44572

Cov.:

show subpopulations

Gnomad AFR

AF:

0.893

Gnomad AMI

AF:

0.659

Gnomad AMR

AF:

0.779

Gnomad ASJ

AF:

0.652

Gnomad EAS

AF:

0.998

Gnomad SAS

AF:

0.858

Gnomad FIN

AF:

0.704

Gnomad MID

AF:

0.601

Gnomad NFE

AF:

0.666

Gnomad OTH

AF:

0.708

GnomAD3 exomes

AF:

0.757

AC:

188057

AN:

248486

Hom.:

72691

AF XY:

0.751

AC XY:

101362

AN XY:

135042

show subpopulations

Gnomad AFR exome

AF:

0.900

Gnomad AMR exome

AF:

0.828

Gnomad ASJ exome

AF:

0.663

Gnomad EAS exome

AF:

0.999

Gnomad SAS exome

AF:

0.850

Gnomad FIN exome

AF:

0.715

Gnomad NFE exome

AF:

0.669

Gnomad OTH exome

AF:

0.697

GnomAD4 exome

AF:

0.708

AC:

1033689

AN:

1460674

Hom.:

370426

Cov.:

AF XY:

0.708

AC XY:

514841

AN XY:

726664

show subpopulations

Gnomad4 AFR exome

AF:

0.896

Gnomad4 AMR exome

AF:

0.820

Gnomad4 ASJ exome

AF:

0.661

Gnomad4 EAS exome

AF:

0.999

Gnomad4 SAS exome

AF:

0.844

Gnomad4 FIN exome

AF:

0.713

Gnomad4 NFE exome

AF:

0.677

Gnomad4 OTH exome

AF:

0.729

GnomAD4 genome

AF:

0.759

AC:

115228

AN:

151758

Hom.:

44627

Cov.:

AF XY:

0.763

AC XY:

56604

AN XY:

74138

show subpopulations

Gnomad4 AFR

AF:

0.893

Gnomad4 AMR

AF:

0.779

Gnomad4 ASJ

AF:

0.652

Gnomad4 EAS

AF:

0.998

Gnomad4 SAS

AF:

0.857

Gnomad4 FIN

AF:

0.704

Gnomad4 NFE

AF:

0.666

Gnomad4 OTH

AF:

0.711

Alfa

AF:

0.695

Hom.:

6233

Asia WGS

AF:

0.928

AC:

3225

AN:

3478

EpiCase

AF:

0.656

EpiControl

AF:

0.652

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Schizophrenia

Benign:1

Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: research

The c.607_608insACA variant in SYNGR1 has been reported in at least 1 individual with schizophrenia (PMID: 17049558), and has been identified in >99% of East Asian chromosomes and 34864 homozygotes by ExAC (http://gnomad.broadinstitute.org/). In summary, this variant meets criteria to be classified as benign for schizophrenia. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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