NM_006950.3:c.1818G>A

Variant names:

Variant summary

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

The NM_006950.3(SYN1):c.1818G>A(p.Gln606Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000952 in 1,050,651 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 3 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0000089 ( 0 hom., 0 hem., cov: 24)

Exomes 𝑓: 0.0000096 ( 0 hom. 3 hem. )

Consequence

SYN1
NM_006950.3 synonymous

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.57

Publications

0 publications found

Variant links:

Genes affected

SYN1 (HGNC:11494): (synapsin I) This gene is a member of the synapsin gene family. Synapsins encode neuronal phosphoproteins which associate with the cytoplasmic surface of synaptic vesicles. Family members are characterized by common protein domains, and they are implicated in synaptogenesis and the modulation of neurotransmitter release, suggesting a potential role in several neuropsychiatric diseases. This member of the synapsin family plays a role in regulation of axonogenesis and synaptogenesis. The protein encoded serves as a substrate for several different protein kinases and phosphorylation may function in the regulation of this protein in the nerve terminal. Mutations in this gene may be associated with X-linked disorders with primary neuronal degeneration such as Rett syndrome. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

SYN1 Gene-Disease associations (from GenCC):

X-linked complex neurodevelopmental disorder
Inheritance: XL Classification: DEFINITIVE Submitted by: ClinGen
epilepsy, X-linked 1, with variable learning disabilities and behavior disorders
Inheritance: XL Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics, Laboratory for Molecular Medicine, G2P
intellectual disability, X-linked 50
Inheritance: XL Classification: STRONG Submitted by: PanelApp Australia

SYN1 links:

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=-0.49).

BP6

Variant X-47574166-C-T is Benign according to our data. Variant chrX-47574166-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 465093.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=2.57 with no splicing effect.

BS2

High Hemizygotes in GnomAdExome4 at 3 XL gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006950.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYN1	NM_006950.3	MANE Select	c.1818G>A	p.Gln606Gln	synonymous	Exon 12 of 13	NP_008881.2	P17600-1
	SYN1	NM_133499.2		c.1818G>A	p.Gln606Gln	synonymous	Exon 12 of 13	NP_598006.1	P17600-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SYN1	ENST00000295987.13	TSL:2 MANE Select	c.1818G>A	p.Gln606Gln	synonymous	Exon 12 of 13	ENSP00000295987.7	P17600-1
SYN1	ENST00000340666.5	TSL:1	c.1818G>A	p.Gln606Gln	synonymous	Exon 12 of 13	ENSP00000343206.4	P17600-2
SYN1	ENST00000950906.1		c.1815G>A	p.Gln605Gln	synonymous	Exon 12 of 13	ENSP00000620965.1

Frequencies

GnomAD3 genomes

AF:

0.00000887

AC:

AN:

112778

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000921

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:

0.000317

AC:

AN:

12616

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00136

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:

0.00000960

AC:

AN:

937873

Hom.:

Cov.:

AF XY:

0.0000102

AC XY:

AN XY:

293645

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

19331

American (AMR)

AF:

0.000777

AC:

AN:

11585

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

13229

East Asian (EAS)

AF:

0.00

AC:

AN:

21649

South Asian (SAS)

AF:

0.00

AC:

AN:

34914

European-Finnish (FIN)

AF:

0.00

AC:

AN:

23496

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2476

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

771857

Other (OTH)

AF:

0.00

AC:

AN:

39336

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.542

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.00000887

AC:

AN:

112778

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

35002

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31163

American (AMR)

AF:

0.0000921

AC:

AN:

10863

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2651

East Asian (EAS)

AF:

0.00

AC:

AN:

3521

South Asian (SAS)

AF:

0.00

AC:

AN:

2786

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6280

Middle Eastern (MID)

AF:

0.00

AC:

AN:

235

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

53084

Other (OTH)

AF:

0.00

AC:

AN:

1520

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000680

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Epilepsy, X-linked 1, with variable learning disabilities and behavior disorders (1)

Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.49

CADD

Benign

(source)

DANN

Benign

0.97

PhyloP100

2.6

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over