X-47619516-C-T

Variant names:

• chrX-47619516-C-T
• rs774873821
• NM_006950.3:c.213G>A

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_Moderate BP6_Moderate BP7

The NM_006950.3(SYN1):​c.213G>A​(p.Ser71Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000669 in 1,196,335 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 (★). Synonymous variant affecting the same amino acid position (i.e. S71S) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0000090 (0 hom., 0 hem., cov: 22)
  • Exomes 𝑓: 0.0000064 (0 hom. 1 hem.)
• Consequence: SYN1 NM_006950.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.55
• 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

ENSG00000283743 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.31).
• BP6: Variant X-47619516-C-T is Benign according to our data. Variant chrX-47619516-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 566777.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.55 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYN1	NM_006950.3	c.213G>A	p.Ser71Ser	synonymous_variant	Exon 1 of 13	ENST00000295987.13	NP_008881.2
SYN1	NM_133499.2	c.213G>A	p.Ser71Ser	synonymous_variant	Exon 1 of 13		NP_598006.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYN1	ENST00000295987.13	c.213G>A	p.Ser71Ser	synonymous_variant	Exon 1 of 13	2	NM_006950.3	ENSP00000295987.7
SYN1	ENST00000340666.5	c.213G>A	p.Ser71Ser	synonymous_variant	Exon 1 of 13	1		ENSP00000343206.4
ENSG00000283743	ENST00000638776.2	n.2833+3574G>A		intron_variant	Intron 7 of 15	5
SYN1	ENST00000639776.1	c.-130G>A		upstream_gene_variant		3		ENSP00000492521.1

Frequencies

GnomAD3 genomes AF: 0.00000902 AC: 1 AN: 110916 Hom.: 0 Cov.: 22

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000190

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000645 AC: 7 AN: 1085419 Hom.: 0 Cov.: 31 AF XY: 0.00000281 AC XY: 1 AN XY: 356319

African (AFR) AF: 0.00 AC: 0 AN: 26055

American (AMR) AF: 0.00 AC: 0 AN: 34740

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19213

East Asian (EAS) AF: 0.00 AC: 0 AN: 29900

South Asian (SAS) AF: 0.00 AC: 0 AN: 53347

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33994

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3701

European-Non Finnish (NFE) AF: 0.00000834 AC: 7 AN: 838840

Other (OTH) AF: 0.00 AC: 0 AN: 45629

GnomAD4 genome AF: 0.00000902 AC: 1 AN: 110916 Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0 AN XY: 33130

African (AFR) AF: 0.00 AC: 0 AN: 30495

American (AMR) AF: 0.00 AC: 0 AN: 10667

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2632

East Asian (EAS) AF: 0.00 AC: 0 AN: 3462

South Asian (SAS) AF: 0.00 AC: 0 AN: 2591

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6124

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 236

European-Non Finnish (NFE) AF: 0.0000190 AC: 1 AN: 52552

Other (OTH) AF: 0.00 AC: 0 AN: 1487

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000151

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

Aug 23, 2022

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.31
CADD	Benign	9.1
DANN	Benign	0.96
PhyloP100		-1.6
PromoterAI		-0.0081	Neutral

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: rs774873821; hg19: chrX-47478915;