rs770195822

Variant names:

• chrX-47574283-T-A
• rs770195822
• NM_006950.3:c.1701A>T

Your query was ambiguous. Multiple possible variants found:

• chrX-47574283-T-A
• chrX-47574283-T-G

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_006950.3(SYN1):​c.1701A>T​(p.Thr567Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000272 in 1,102,205 control chromosomes in the GnomAD database, including 1 homozygotes. There are 92 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 0.00044 (0 hom., 17 hem., cov: 23)
  • Exomes 𝑓: 0.00025 (1 hom. 75 hem.)
• Consequence: SYN1 NM_006950.3 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.364
• 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: Benign. The variant received -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.62).
• BP6: Variant X-47574283-T-A is Benign according to our data. Variant chrX-47574283-T-A is described in ClinVar as Likely_benign. ClinVar VariationId is 465092.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.364 with no splicing effect.
• BS2: High Hemizygotes in GnomAd4 at 17 XL gene

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.1701A>T	p.Thr567Thr	synonymous	Exon 12 of 13	NP_008881.2
	SYN1	NM_133499.2		c.1701A>T	p.Thr567Thr	synonymous	Exon 12 of 13	NP_598006.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYN1	ENST00000295987.13	TSL:2 MANE Select	c.1701A>T	p.Thr567Thr	synonymous	Exon 12 of 13	ENSP00000295987.7
	SYN1	ENST00000340666.5	TSL:1	c.1701A>T	p.Thr567Thr	synonymous	Exon 12 of 13	ENSP00000343206.4
	SYN1	ENST00000950906.1		c.1698A>T	p.Thr566Thr	synonymous	Exon 12 of 13	ENSP00000620965.1

Frequencies

GnomAD3 genomes AF: 0.000438 AC: 49 AN: 111773 Hom.: 0 Cov.: 23

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: 0.00295

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000587

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000222 AC: 12 AN: 54143 AF XY: 0.0000538

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: 0.000854

Gnomad NFE exome AF: 0.000455

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000253 AC: 251 AN: 990432 Hom.: 1 Cov.: 32 AF XY: 0.000235 AC XY: 75 AN XY: 319216

African (AFR) AF: 0.00 AC: 0 AN: 21065

American (AMR) AF: 0.00 AC: 0 AN: 21072

Ashkenazi Jewish (ASJ) AF: 0.000117 AC: 2 AN: 17029

East Asian (EAS) AF: 0.00 AC: 0 AN: 21854

South Asian (SAS) AF: 0.00 AC: 0 AN: 44122

European-Finnish (FIN) AF: 0.00239 AC: 60 AN: 25080

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2734

European-Non Finnish (NFE) AF: 0.000220 AC: 175 AN: 795774

Other (OTH) AF: 0.000336 AC: 14 AN: 41702

GnomAD4 genome AF: 0.000438 AC: 49 AN: 111773 Hom.: 0 Cov.: 23 AF XY: 0.000497 AC XY: 17 AN XY: 34237

African (AFR) AF: 0.00 AC: 0 AN: 30780

American (AMR) AF: 0.00 AC: 0 AN: 10812

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2642

East Asian (EAS) AF: 0.00 AC: 0 AN: 3475

South Asian (SAS) AF: 0.00 AC: 0 AN: 2772

European-Finnish (FIN) AF: 0.00295 AC: 18 AN: 6095

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 230

European-Non Finnish (NFE) AF: 0.000587 AC: 31 AN: 52793

Other (OTH) AF: 0.00 AC: 0 AN: 1512

Alfa AF: 0.000864 Hom.: 3

Bravo AF: 0.000125

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Epilepsy, X-linked 1, with variable learning disabilities and behavior disorders (1)
-	-	1	Inborn genetic diseases (1)
-	-	1	not provided (1)
-	-	1	SYN1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	7.3
DANN	Benign	0.81
PhyloP100		-0.36
PromoterAI		0.31	Neutral
Mutation Taster		=100/0	polymorphism

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: rs770195822; hg19: chrX-47433682;