NM_006950.3:c.1137C>T

Variant names:

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_006950.3(SYN1):c.1137C>T(p.Asp379Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000566 in 1,200,983 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 25 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 0.000063 ( 0 hom., 1 hem., cov: 23)

Exomes 𝑓: 0.000056 ( 0 hom. 24 hem. )

Consequence

SYN1
NM_006950.3 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.843

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: 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 -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.61).

BP6

Variant X-47576152-G-A is Benign according to our data. Variant chrX-47576152-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 465086.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.843 with no splicing effect.

BS2

High Hemizygotes in GnomAdExome4 at 24 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYN1	NM_006950.3 link	c.1137C>T	p.Asp379Asp	synonymous_variant	Exon 9 of 13	ENST00000295987.13	NP_008881.2	P17600-1
SYN1	NM_133499.2 link	c.1137C>T	p.Asp379Asp	synonymous_variant	Exon 9 of 13		NP_598006.1	P17600-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SYN1	ENST00000295987.13 link	c.1137C>T	p.Asp379Asp	synonymous_variant	Exon 9 of 13	2	NM_006950.3	ENSP00000295987.7	P17600-1
SYN1	ENST00000340666.5 link	c.1137C>T	p.Asp379Asp	synonymous_variant	Exon 9 of 13	1		ENSP00000343206.4	P17600-2
ENSG00000283743	ENST00000638776.2 link	n.3593C>T		non_coding_transcript_exon_variant	Exon 15 of 16	5

Frequencies

GnomAD3 genomes

AF:

0.0000626

AC:

AN:

111743

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000369

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000113

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000185

AC:

AN:

161748

AF XY:

0.0000196

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000427

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000560

AC:

AN:

1089240

Hom.:

Cov.:

AF XY:

0.0000672

AC XY:

AN XY:

356898

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26137

American (AMR)

AF:

0.00

AC:

AN:

34190

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19259

East Asian (EAS)

AF:

0.00

AC:

AN:

29783

South Asian (SAS)

AF:

0.0000190

AC:

AN:

52580

European-Finnish (FIN)

AF:

0.00

AC:

AN:

39896

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4123

European-Non Finnish (NFE)

AF:

0.0000561

AC:

AN:

837503

Other (OTH)

AF:

0.000284

AC:

AN:

45769

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

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:

0.0000626

AC:

AN:

111743

Hom.:

Cov.:

AF XY:

0.0000295

AC XY:

AN XY:

33933

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30713

American (AMR)

AF:

0.00

AC:

AN:

10597

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2646

East Asian (EAS)

AF:

0.00

AC:

AN:

3582

South Asian (SAS)

AF:

0.000369

AC:

AN:

2711

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6000

Middle Eastern (MID)

AF:

0.00

AC:

AN:

237

European-Non Finnish (NFE)

AF:

0.000113

AC:

AN:

53078

Other (OTH)

AF:

0.00

AC:

AN:

1500

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.000130

Hom.:

Bravo

AF:

0.0000453

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

Sep 04, 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

BayesDel_noAF

Benign

-0.61

CADD

Benign

0.050

(source)

DANN

Benign

0.66

PhyloP100

-0.84

Mutation Taster

=97/3

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

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over