rs6520278

Variant names:

• chrX-47588525-C-T
• rs6520278
• NM_006950.3:c.775-11024G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006950.3(SYN1):​c.775-11024G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.355 in 110,915 control chromosomes in the GnomAD database, including 5,026 homozygotes. There are 11,536 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.35 (5026 hom., 11536 hem., cov: 23)
• Consequence: SYN1 NM_006950.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.72
• Publications: 10 publications found

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

ENSG00000283743 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.437 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYN1	NM_006950.3	c.775-11024G>A		intron_variant	Intron 5 of 12	ENST00000295987.13	NP_008881.2
SYN1	NM_133499.2	c.775-11024G>A		intron_variant	Intron 5 of 12		NP_598006.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYN1	ENST00000295987.13	c.775-11024G>A		intron_variant	Intron 5 of 12	2	NM_006950.3	ENSP00000295987.7
SYN1	ENST00000340666.5	c.775-11024G>A		intron_variant	Intron 5 of 12	1		ENSP00000343206.4
ENSG00000283743	ENST00000638776.2	n.3231-11024G>A		intron_variant	Intron 11 of 15	5

Frequencies

GnomAD3 genomes AF: 0.355 AC: 39338 AN: 110860 Hom.: 5022 Cov.: 23

Gnomad AFR AF: 0.382

Gnomad AMI AF: 0.362

Gnomad AMR AF: 0.287

Gnomad ASJ AF: 0.365

Gnomad EAS AF: 0.382

Gnomad SAS AF: 0.459

Gnomad FIN AF: 0.345

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.347

Gnomad OTH AF: 0.344

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.355 AC: 39357 AN: 110915 Hom.: 5026 Cov.: 23 AF XY: 0.348 AC XY: 11536 AN XY: 33167

African (AFR) AF: 0.382 AC: 11638 AN: 30489

American (AMR) AF: 0.287 AC: 3011 AN: 10495

Ashkenazi Jewish (ASJ) AF: 0.365 AC: 954 AN: 2616

East Asian (EAS) AF: 0.382 AC: 1337 AN: 3497

South Asian (SAS) AF: 0.458 AC: 1213 AN: 2647

European-Finnish (FIN) AF: 0.345 AC: 2040 AN: 5918

Middle Eastern (MID) AF: 0.319 AC: 69 AN: 216

European-Non Finnish (NFE) AF: 0.347 AC: 18326 AN: 52838

Other (OTH) AF: 0.344 AC: 522 AN: 1517

Alfa AF: 0.352 Hom.: 41893

Bravo AF: 0.356

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.065
DANN	Benign	0.57
PhyloP100		-1.7
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6520278; hg19: chrX-47447924;