rs6520278

Positions:

• chrX-47588525-C-T

Variant summary

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

The NM_006950.3(SYN1):​c.775-11024G>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

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]

ENSG00000283743 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
SYN1	NM_006950.3	c.775-11024G>A		intron_variant		ENST00000295987.13	NP_008881.2
SYN1	NM_133499.2	c.775-11024G>A		intron_variant			NP_598006.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SYN1	ENST00000295987.13	c.775-11024G>A		intron_variant		2	NM_006950.3	ENSP00000295987.7
SYN1	ENST00000340666.5	c.775-11024G>A		intron_variant		1		ENSP00000343206.4
ENSG00000283743	ENST00000638776.2	n.3231-11024G>A		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.355 AC: 39338 AN: 110860 Hom.: 5022 Cov.: 23 AF XY: 0.348 AC XY: 11522 AN XY: 33102

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

Gnomad4 AFR AF: 0.382

Gnomad4 AMR AF: 0.287

Gnomad4 ASJ AF: 0.365

Gnomad4 EAS AF: 0.382

Gnomad4 SAS AF: 0.458

Gnomad4 FIN AF: 0.345

Gnomad4 NFE AF: 0.347

Gnomad4 OTH AF: 0.344

Alfa AF: 0.351 Hom.: 31374

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

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: rs6520278; hg19: chrX-47447924;