X-47587120-T-G

Variant names:

• chrX-47587120-T-G
• rs2070584
• NM_006950.3:c.775-9619A>C

Variant summary

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

The NM_006950.3(SYN1):​c.775-9619A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.442 in 111,830 control chromosomes in the GnomAD database, including 7,745 homozygotes. There are 14,920 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 0.44 (7745 hom., 14920 hem., cov: 24)
• Consequence: SYN1 NM_006950.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.319
• Publications: 32 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=-0.8).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.49 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.775-9619A>C		intron	N/A	NP_008881.2	P17600-1
	SYN1	NM_133499.2		c.775-9619A>C		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.775-9619A>C		intron	N/A	ENSP00000295987.7	P17600-1
	SYN1	ENST00000340666.5	TSL:1	c.775-9619A>C		intron	N/A	ENSP00000343206.4	P17600-2
	SYN1	ENST00000950906.1		c.775-9619A>C		intron	N/A	ENSP00000620965.1

Frequencies

GnomAD3 genomes AF: 0.442 AC: 49438 AN: 111774 Hom.: 7736 Cov.: 24

Gnomad AFR AF: 0.429

Gnomad AMI AF: 0.394

Gnomad AMR AF: 0.431

Gnomad ASJ AF: 0.437

Gnomad EAS AF: 0.436

Gnomad SAS AF: 0.513

Gnomad FIN AF: 0.439

Gnomad MID AF: 0.362

Gnomad NFE AF: 0.451

Gnomad OTH AF: 0.441

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

GnomAD4 genome AF: 0.442 AC: 49478 AN: 111830 Hom.: 7745 Cov.: 24 AF XY: 0.438 AC XY: 14920 AN XY: 34052

African (AFR) AF: 0.430 AC: 13219 AN: 30762

American (AMR) AF: 0.431 AC: 4587 AN: 10648

Ashkenazi Jewish (ASJ) AF: 0.437 AC: 1157 AN: 2646

East Asian (EAS) AF: 0.436 AC: 1540 AN: 3529

South Asian (SAS) AF: 0.512 AC: 1388 AN: 2710

European-Finnish (FIN) AF: 0.439 AC: 2656 AN: 6057

Middle Eastern (MID) AF: 0.352 AC: 77 AN: 219

European-Non Finnish (NFE) AF: 0.451 AC: 23901 AN: 53042

Other (OTH) AF: 0.446 AC: 685 AN: 1537

Alfa AF: 0.445 Hom.: 31042

Bravo AF: 0.444

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	4.4
DANN	Benign	0.81
PhyloP100		-0.32
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: rs2070584; hg19: chrX-47446519;