X-47576539-G-A

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.939C>T​(p.Asp313Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000393 in 1,210,166 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 139 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 0.00021 ( 0 hom., 2 hem., cov: 23)
Exomes 𝑓: 0.00041 ( 0 hom. 137 hem. )

Consequence

SYN1
NM_006950.3 synonymous

Scores

2

Clinical Significance

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

Conservation

PhyloP100: 1.04

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

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=-0.57).
BP6
Variant X-47576539-G-A is Benign according to our data. Variant chrX-47576539-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 465102.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=1.04 with no splicing effect.
BS2
High Hemizygotes in GnomAd4 at 2 XL gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SYN1NM_006950.3 linkc.939C>T p.Asp313Asp synonymous_variant Exon 7 of 13 ENST00000295987.13 NP_008881.2 P17600-1
SYN1NM_133499.2 linkc.939C>T p.Asp313Asp synonymous_variant Exon 7 of 13 NP_598006.1 P17600-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SYN1ENST00000295987.13 linkc.939C>T p.Asp313Asp synonymous_variant Exon 7 of 13 2 NM_006950.3 ENSP00000295987.7 P17600-1
SYN1ENST00000340666.5 linkc.939C>T p.Asp313Asp synonymous_variant Exon 7 of 13 1 ENSP00000343206.4 P17600-2
ENSG00000283743ENST00000638776.2 linkn.3395C>T non_coding_transcript_exon_variant Exon 13 of 16 5

Frequencies

GnomAD3 genomes
AF:
0.000206
AC:
23
AN:
111857
Hom.:
0
Cov.:
23
show subpopulations
Gnomad AFR
AF:
0.000195
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000283
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:
0.000263
Gnomad OTH
AF:
0.00
GnomAD2 exomes
AF:
0.000153
AC:
28
AN:
183514
AF XY:
0.000118
show subpopulations
Gnomad AFR exome
AF:
0.000228
Gnomad AMR exome
AF:
0.000182
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000232
Gnomad OTH exome
AF:
0.000221
GnomAD4 exome
AF:
0.000412
AC:
453
AN:
1098254
Hom.:
0
Cov.:
33
AF XY:
0.000377
AC XY:
137
AN XY:
363608
show subpopulations
African (AFR)
AF:
0.000114
AC:
3
AN:
26403
American (AMR)
AF:
0.000170
AC:
6
AN:
35207
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
19386
East Asian (EAS)
AF:
0.00
AC:
0
AN:
30206
South Asian (SAS)
AF:
0.00
AC:
0
AN:
54149
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
40533
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
4135
European-Non Finnish (NFE)
AF:
0.000508
AC:
428
AN:
842137
Other (OTH)
AF:
0.000347
AC:
16
AN:
46098
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.464
Heterozygous variant carriers
0
22
44
67
89
111
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
20
40
60
80
100
<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:
0.000206
AC:
23
AN:
111912
Hom.:
0
Cov.:
23
AF XY:
0.0000586
AC XY:
2
AN XY:
34106
show subpopulations
African (AFR)
AF:
0.000195
AC:
6
AN:
30760
American (AMR)
AF:
0.000283
AC:
3
AN:
10607
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
2651
East Asian (EAS)
AF:
0.00
AC:
0
AN:
3562
South Asian (SAS)
AF:
0.00
AC:
0
AN:
2689
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
6035
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
217
European-Non Finnish (NFE)
AF:
0.000263
AC:
14
AN:
53186
Other (OTH)
AF:
0.00
AC:
0
AN:
1524
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.506
Heterozygous variant carriers
0
1
2
3
4
5
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
2
4
6
8
10
<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:
0.000142
Hom.:
1
Bravo
AF:
0.000212
EpiCase
AF:
0.000164
EpiControl
AF:
0.000237

ClinVar

Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

Epilepsy, X-linked 1, with variable learning disabilities and behavior disorders Benign:1
Nov 11, 2024
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

History of neurodevelopmental disorder Benign:1
Dec 12, 2016
Ambry Genetics
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

Synonymous alterations with insufficient evidence to classify as benign -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.57
CADD
Benign
4.3
DANN
Benign
0.75
PhyloP100
1.0
Mutation Taster
=100/0
polymorphism

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.10
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs373928763; hg19: chrX-47435938; API