rs6609534

chrX-47587254-G-AchrX-47587254-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006950.3(SYN1):c.775-9753C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.289 in 111,453 control chromosomes in the GnomAD database, including 3,598 homozygotes. There are 9,702 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 0.29 (3598 hom., 9702 hem., cov: 23)
• Consequence: SYN1 NM_006950.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.825

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.439 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SYN1	NM_006950.3	c.775-9753C>T		intron_variant		ENST00000295987.13
SYN1	NM_133499.2	c.775-9753C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SYN1	ENST00000295987.13	c.775-9753C>T		intron_variant		2	NM_006950.3	P3
SYN1	ENST00000340666.5	c.775-9753C>T		intron_variant		1		A1

Frequencies

GnomAD3 genomes AF: 0.289 AC: 32171 AN: 111397 Hom.: 3596 Cov.: 23 AF XY: 0.288 AC XY: 9693 AN XY: 33647

Gnomad AFR AF: 0.149

Gnomad AMI AF: 0.357

Gnomad AMR AF: 0.262

Gnomad ASJ AF: 0.360

Gnomad EAS AF: 0.411

Gnomad SAS AF: 0.460

Gnomad FIN AF: 0.346

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.348

Gnomad OTH AF: 0.287

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

GnomAD4 genome AF: 0.289 AC: 32179 AN: 111453 Hom.: 3598 Cov.: 23 AF XY: 0.288 AC XY: 9702 AN XY: 33713

Gnomad4 AFR AF: 0.149

Gnomad4 AMR AF: 0.263

Gnomad4 ASJ AF: 0.360

Gnomad4 EAS AF: 0.411

Gnomad4 SAS AF: 0.460

Gnomad4 FIN AF: 0.346

Gnomad4 NFE AF: 0.348

Gnomad4 OTH AF: 0.288

Alfa AF: 0.302 Hom.: 2734

Bravo AF: 0.280

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	5.1
Dann	Benign	0.80

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

LitVar

Other links and lift over

dbSNP: rs6609534; hg19: chrX-47446653;