rs372165835

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP6_ModerateBS2

The NM_006950.3(SYN1):c.360C>A(p.Asp120Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00001 in 1,196,930 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 4 hemizygotes in GnomAD. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000045 ( 0 hom., 2 hem., cov: 22)

Exomes 𝑓: 0.0000065 ( 0 hom. 2 hem. )

Consequence

SYN1
NM_006950.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.422

Publications

1 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: Likely_benign. The variant received -6 ACMG points.

BP6

Variant X-47619369-G-T is Benign according to our data. Variant chrX-47619369-G-T is described in ClinVar as Likely_benign. ClinVar VariationId is 465097.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAd4 at 2 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYN1	NM_006950.3 link	c.360C>A	p.Asp120Glu	missense_variant	Exon 1 of 13	ENST00000295987.13	NP_008881.2	P17600-1
SYN1	NM_133499.2 link	c.360C>A	p.Asp120Glu	missense_variant	Exon 1 of 13		NP_598006.1	P17600-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SYN1	ENST00000295987.13 link	c.360C>A	p.Asp120Glu	missense_variant	Exon 1 of 13	2	NM_006950.3	ENSP00000295987.7	P17600-1
SYN1	ENST00000340666.5 link	c.360C>A	p.Asp120Glu	missense_variant	Exon 1 of 13	1		ENSP00000343206.4	P17600-2
SYN1	ENST00000639776.1 link	c.18C>A	p.Asp6Glu	missense_variant	Exon 1 of 6	3		ENSP00000492521.1	A0A1W2PS00
ENSG00000283743	ENST00000638776.2 link	n.2833+3721C>A		intron_variant	Intron 7 of 15	5

Frequencies

GnomAD3 genomes

AF:

0.0000445

AC:

AN:

112301

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000129

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000927

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:

0.0000326

AC:

AN:

153289

AF XY:

0.0000185

show subpopulations

Gnomad AFR exome

AF:

0.000303

Gnomad AMR exome

AF:

0.0000761

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:

0.00000645

AC:

AN:

1084629

Hom.:

Cov.:

AF XY:

0.00000560

AC XY:

AN XY:

357117

show subpopulations

African (AFR)

AF:

0.000114

AC:

AN:

26287

American (AMR)

AF:

0.0000574

AC:

AN:

34854

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19247

East Asian (EAS)

AF:

0.00

AC:

AN:

30052

South Asian (SAS)

AF:

0.00

AC:

AN:

53317

European-Finnish (FIN)

AF:

0.00

AC:

AN:

32078

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2908

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

840218

Other (OTH)

AF:

0.0000438

AC:

AN:

45668

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.545

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:

0.0000445

AC:

AN:

112301

Hom.:

Cov.:

AF XY:

0.0000581

AC XY:

AN XY:

34453

show subpopulations

African (AFR)

AF:

0.000129

AC:

AN:

30910

American (AMR)

AF:

0.0000927

AC:

AN:

10791

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2651

East Asian (EAS)

AF:

0.00

AC:

AN:

3530

South Asian (SAS)

AF:

0.00

AC:

AN:

2720

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6257

Middle Eastern (MID)

AF:

0.00

AC:

AN:

238

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

53014

Other (OTH)

AF:

0.00

AC:

AN:

1510

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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

Alfa

AF:

0.0000868

Hom.:

Bravo

AF:

0.0000907

ESP6500AA

AF:

0.000297

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00000853

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

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

Benign:1

Jun 05, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.94

BayesDel_addAF

Benign

-0.039

BayesDel_noAF

Benign

-0.29

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Pathogenic

0.82

D;.

FATHMM_MKL

Benign

0.41

LIST_S2

Uncertain

0.92

D;D

M_CAP

Pathogenic

0.63

MetaRNN

Uncertain

0.74

D;D

MetaSVM

Benign

-0.62

MutationAssessor

Uncertain

2.0

M;M

PhyloP100

-0.42

PrimateAI

Pathogenic

0.85

PROVEAN

Uncertain

-3.2

D;D

REVEL

Uncertain

0.36

Sift

Uncertain

0.0020

D;D

Sift4G

Uncertain

0.0040

D;D

Polyphen

0.92

P;D

Vest4

0.67

MutPred

0.92

Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);

MVP

0.71

MPC

1.5

ClinPred

0.40

GERP RS

-1.1

PromoterAI

-0.029

Neutral

(source)

Varity_R

0.71

gMVP

0.77

Mutation Taster

=87/13

polymorphism

(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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over