rs1452773137

Variant names:

• chrX-47574169-G-A
• rs1452773137
• NM_006950.3:c.1815C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_006950.3(SYN1):​c.1815C>T​(p.Ser605Ser) variant causes a synonymous change. The variant allele was found at a frequency of 0.00000285 in 1,052,632 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0000089 (0 hom., 0 hem., cov: 23)
  • Exomes 𝑓: 0.0000021 (0 hom. 1 hem.)
• Consequence: SYN1 NM_006950.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.36
• Publications: 0 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

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BP6: Variant X-47574169-G-A is Benign according to our data. Variant chrX-47574169-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 533665.Status of the report is criteria_provided_single_submitter, 1 stars.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYN1	NM_006950.3	MANE Select	c.1815C>T	p.Ser605Ser	synonymous	Exon 12 of 13	NP_008881.2
	SYN1	NM_133499.2		c.1815C>T	p.Ser605Ser	synonymous	Exon 12 of 13	NP_598006.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYN1	ENST00000295987.13	TSL:2 MANE Select	c.1815C>T	p.Ser605Ser	synonymous	Exon 12 of 13	ENSP00000295987.7
	SYN1	ENST00000340666.5	TSL:1	c.1815C>T	p.Ser605Ser	synonymous	Exon 12 of 13	ENSP00000343206.4
	SYN1	ENST00000640721.1	TSL:5	c.70+519C>T		intron	N/A	ENSP00000492857.1

Frequencies

GnomAD3 genomes AF: 0.00000886 AC: 1 AN: 112920 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000918

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00 AC: 0 AN: 13276 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000213 AC: 2 AN: 939667 Hom.: 0 Cov.: 32 AF XY: 0.00000339 AC XY: 1 AN XY: 294861

African (AFR) AF: 0.00 AC: 0 AN: 19375

American (AMR) AF: 0.00 AC: 0 AN: 11729

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13338

East Asian (EAS) AF: 0.0000461 AC: 1 AN: 21669

South Asian (SAS) AF: 0.00 AC: 0 AN: 35301

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 23570

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2487

European-Non Finnish (NFE) AF: 0.00000129 AC: 1 AN: 772797

Other (OTH) AF: 0.00 AC: 0 AN: 39401

GnomAD4 genome AF: 0.00000885 AC: 1 AN: 112965 Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0 AN XY: 35179

African (AFR) AF: 0.00 AC: 0 AN: 31263

American (AMR) AF: 0.0000917 AC: 1 AN: 10906

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2654

East Asian (EAS) AF: 0.00 AC: 0 AN: 3512

South Asian (SAS) AF: 0.00 AC: 0 AN: 2785

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6308

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 216

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 53109

Other (OTH) AF: 0.00 AC: 0 AN: 1538

Alfa AF: 0.00 Hom.: 0

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Epilepsy, X-linked 1, with variable learning disabilities and behavior disorders Benign:1

Mar 02, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	13
DANN	Benign	0.97
PhyloP100		4.4

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: rs1452773137; hg19: chrX-47433568;