X-47606962-A-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_006950.3(SYN1):c.510T>C(p.Asn170Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.378 in 1,205,344 control chromosomes in the GnomAD database, including 59,194 homozygotes. There are 147,047 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.39 ( 6121 hom., 11667 hem., cov: 21)

Exomes 𝑓: 0.38 ( 53073 hom. 135380 hem. )

Consequence

SYN1
NM_006950.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: 1.29

Publications

20 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: Ambry Genetics, G2P, Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae), Orphanet

SYN1 links:

ENSG00000283743 (HGNC:):

ENSG00000283743 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.53).

BP6

Variant X-47606962-A-G is Benign according to our data. Variant chrX-47606962-A-G is described in ClinVar as Benign. ClinVar VariationId is 96364.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.29 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.415 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYN1	NM_006950.3	MANE Select	c.510T>C	p.Asn170Asn	synonymous	Exon 3 of 13	NP_008881.2
	SYN1	NM_133499.2		c.510T>C	p.Asn170Asn	synonymous	Exon 3 of 13	NP_598006.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
SYN1	ENST00000295987.13	TSL:2 MANE Select	c.510T>C	p.Asn170Asn	synonymous	Exon 3 of 13	ENSP00000295987.7
SYN1	ENST00000340666.5	TSL:1	c.510T>C	p.Asn170Asn	synonymous	Exon 3 of 13	ENSP00000343206.4
SYN1	ENST00000639776.1	TSL:3	c.168T>C	p.Asn56Asn	synonymous	Exon 3 of 6	ENSP00000492521.1

Frequencies

GnomAD3 genomes

AF:

0.390

AC:

42238

AN:

108421

Hom.:

6119

Cov.:

show subpopulations

Gnomad AFR

AF:

0.421

Gnomad AMI

AF:

0.392

Gnomad AMR

AF:

0.396

Gnomad ASJ

AF:

0.395

Gnomad EAS

AF:

0.254

Gnomad SAS

AF:

0.308

Gnomad FIN

AF:

0.370

Gnomad MID

AF:

0.364

Gnomad NFE

AF:

0.385

Gnomad OTH

AF:

0.402

GnomAD2 exomes

AF:

0.371

AC:

67286

AN:

181327

AF XY:

0.360

show subpopulations

Gnomad AFR exome

AF:

0.423

Gnomad AMR exome

AF:

0.394

Gnomad ASJ exome

AF:

0.398

Gnomad EAS exome

AF:

0.258

Gnomad FIN exome

AF:

0.390

Gnomad NFE exome

AF:

0.381

Gnomad OTH exome

AF:

0.366

GnomAD4 exome

AF:

0.376

AC:

412886

AN:

1096885

Hom.:

53073

Cov.:

AF XY:

0.374

AC XY:

135380

AN XY:

362439

show subpopulations

African (AFR)

AF:

0.421

AC:

11115

AN:

26391

American (AMR)

AF:

0.396

AC:

13891

AN:

35068

Ashkenazi Jewish (ASJ)

AF:

0.394

AC:

7629

AN:

19372

East Asian (EAS)

AF:

0.203

AC:

6126

AN:

30182

South Asian (SAS)

AF:

0.320

AC:

17299

AN:

54063

European-Finnish (FIN)

AF:

0.388

AC:

15679

AN:

40432

Middle Eastern (MID)

AF:

0.368

AC:

1518

AN:

4130

European-Non Finnish (NFE)

AF:

0.383

AC:

322150

AN:

841215

Other (OTH)

AF:

0.380

AC:

17479

AN:

46032

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

9437

18875

28312

37750

47187

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10936

21872

32808

43744

54680

<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:

0.390

AC:

42256

AN:

108459

Hom.:

6121

Cov.:

AF XY:

0.379

AC XY:

11667

AN XY:

30819

show subpopulations

African (AFR)

AF:

0.421

AC:

12486

AN:

29643

American (AMR)

AF:

0.396

AC:

3991

AN:

10087

Ashkenazi Jewish (ASJ)

AF:

0.395

AC:

1030

AN:

2608

East Asian (EAS)

AF:

0.254

AC:

871

AN:

3424

South Asian (SAS)

AF:

0.306

AC:

762

AN:

2492

European-Finnish (FIN)

AF:

0.370

AC:

2033

AN:

5497

Middle Eastern (MID)

AF:

0.355

AC:

AN:

217

European-Non Finnish (NFE)

AF:

0.385

AC:

20150

AN:

52361

Other (OTH)

AF:

0.406

AC:

595

AN:

1465

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

939

1878

2817

3756

4695

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

404

808

1212

1616

2020

<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:

0.389

Hom.:

18572

Bravo

AF:

0.396

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

Apr 20, 2017

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

not specified

Benign:2

Genetic Services Laboratory, University of Chicago

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed.

Nov 19, 2013

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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

Benign:2

Jul 15, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Intellectual disability, X-linked 50

Benign:1

Jul 15, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

History of neurodevelopmental disorder

Benign:1

Apr 15, 2016

Ambry Genetics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This alteration is classified as benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.53

CADD

Benign

2.0

(source)

DANN

Benign

0.45

PhyloP100

1.3

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over