dbSNP rs767722750: SYN1:c.1159-7C>T (chrX-47575281-G-A) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_006950.3(SYN1):c.1159-7C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000073 in 1,095,448 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 4 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 24)

Exomes 𝑓: 0.0000073 ( 0 hom. 4 hem. )

Consequence

SYN1
NM_006950.3 splice_region, intron

Scores

Splicing: ADA: 0.00002932

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.560

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 links:

ENSG00000283743 (HGNC:):

ENSG00000283743 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant X-47575281-G-A is Benign according to our data. Variant chrX-47575281-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 533666.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAdExome4 at 4 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYN1	NM_006950.3 link	c.1159-7C>T		splice_region_variant, intron_variant	Intron 9 of 12	ENST00000295987.13	NP_008881.2	P17600-1
SYN1	NM_133499.2 link	c.1159-7C>T		splice_region_variant, intron_variant	Intron 9 of 12		NP_598006.1	P17600-2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
SYN1	ENST00000295987.13 link	c.1159-7C>T	splice_region_variant, intron_variant	Intron 9 of 12	2	NM_006950.3	ENSP00000295987.7	P17600-1
SYN1	ENST00000340666.5 link	c.1159-7C>T	splice_region_variant, intron_variant	Intron 9 of 12	1		ENSP00000343206.4	P17600-2
ENSG00000283743	ENST00000638776.2 link	n.3615-7C>T	splice_region_variant, intron_variant	Intron 15 of 15	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000114

AC:

AN:

175061

Hom.:

AF XY:

0.0000164

AC XY:

AN XY:

60889

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000740

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000128

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000730

AC:

AN:

1095448

Hom.:

Cov.:

AF XY:

0.0000111

AC XY:

AN XY:

361008

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000143

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000332

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000435

GnomAD4 genome

Cov.:

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

Jan 14, 2025

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

-0.80

CADD

Benign

5.0

DANN

Benign

0.87

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000029

dbscSNV1_RF

Benign

0.0020

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over