X-47589011-C-T

Variant names:

• chrX-47589011-C-T
• rs5906435
• NM_006950.3:c.775-11510G>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.775-11510G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.277 in 110,486 control chromosomes in the GnomAD database, including 3,633 homozygotes. There are 9,022 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 0.28 (3633 hom., 9022 hem., cov: 22)
• Consequence: SYN1 NM_006950.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.65
• Publications: 7 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: Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics, Laboratory for Molecular Medicine, G2P
• intellectual disability, X-linked 50

  Inheritance: XL Classification: STRONG Submitted by: PanelApp Australia

ENSG00000283743 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.421 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006950.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYN1	NM_006950.3	MANE Select	c.775-11510G>A		intron	N/A	NP_008881.2	P17600-1
	SYN1	NM_133499.2		c.775-11510G>A		intron	N/A	NP_598006.1	P17600-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYN1	ENST00000295987.13	TSL:2 MANE Select	c.775-11510G>A		intron	N/A	ENSP00000295987.7	P17600-1
	SYN1	ENST00000340666.5	TSL:1	c.775-11510G>A		intron	N/A	ENSP00000343206.4	P17600-2
	SYN1	ENST00000950906.1		c.775-11510G>A		intron	N/A	ENSP00000620965.1

Frequencies

GnomAD3 genomes AF: 0.277 AC: 30609 AN: 110431 Hom.: 3631 Cov.: 22

Gnomad AFR AF: 0.0898

Gnomad AMI AF: 0.400

Gnomad AMR AF: 0.265

Gnomad ASJ AF: 0.381

Gnomad EAS AF: 0.376

Gnomad SAS AF: 0.441

Gnomad FIN AF: 0.379

Gnomad MID AF: 0.325

Gnomad NFE AF: 0.355

Gnomad OTH AF: 0.284

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

GnomAD4 genome AF: 0.277 AC: 30611 AN: 110486 Hom.: 3633 Cov.: 22 AF XY: 0.276 AC XY: 9022 AN XY: 32710

African (AFR) AF: 0.0896 AC: 2739 AN: 30561

American (AMR) AF: 0.265 AC: 2758 AN: 10392

Ashkenazi Jewish (ASJ) AF: 0.381 AC: 1002 AN: 2630

East Asian (EAS) AF: 0.375 AC: 1307 AN: 3481

South Asian (SAS) AF: 0.442 AC: 1146 AN: 2590

European-Finnish (FIN) AF: 0.379 AC: 2186 AN: 5765

Middle Eastern (MID) AF: 0.329 AC: 71 AN: 216

European-Non Finnish (NFE) AF: 0.355 AC: 18706 AN: 52680

Other (OTH) AF: 0.285 AC: 426 AN: 1496

Alfa AF: 0.222 Hom.: 1611

Bravo AF: 0.265

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	7.9
DANN	Benign	0.90
PhyloP100		1.6
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: rs5906435; hg19: chrX-47448410;