rs141925310

chrX-47576179-G-AchrX-47576179-G-C

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_006950.3(SYN1):c.1110C>T(p.Cys370=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000185 in 1,202,995 control chromosomes in the GnomAD database, including 1 homozygotes. There are 52 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 0.00095 (1 hom., 23 hem., cov: 23)
  • Exomes 𝑓: 0.00011 (0 hom. 29 hem.)
• Consequence: SYN1 NM_006950.3 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.976

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]

ACMG classification

Verdict is Benign. Variant got -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP6: Variant X-47576179-G-A is Benign according to our data. Variant chrX-47576179-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 207463.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.976 with no splicing effect.
• BS2: High Hemizygotes in GnomAd at 22 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SYN1	NM_006950.3	c.1110C>T	p.Cys370=	synonymous_variant	9/13	ENST00000295987.13
SYN1	NM_133499.2	c.1110C>T	p.Cys370=	synonymous_variant	9/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SYN1	ENST00000295987.13	c.1110C>T	p.Cys370=	synonymous_variant	9/13	2	NM_006950.3	P3
SYN1	ENST00000340666.5	c.1110C>T	p.Cys370=	synonymous_variant	9/13	1		A1

Frequencies

GnomAD3 genomes AF: 0.000939 AC: 105 AN: 111866 Hom.: 1 Cov.: 23 AF XY: 0.000646 AC XY: 22 AN XY: 34048

Gnomad AFR AF: 0.00326

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000377

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: 0.0000188

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000345 AC: 57 AN: 165446 Hom.: 0 AF XY: 0.000150 AC XY: 8 AN XY: 53314

Gnomad AFR exome AF: 0.00448

Gnomad AMR exome AF: 0.000115

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000138

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000106 AC: 116 AN: 1091076 Hom.: 0 Cov.: 32 AF XY: 0.0000810 AC XY: 29 AN XY: 357830

Gnomad4 AFR exome AF: 0.00362

Gnomad4 AMR exome AF: 0.000116

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000107

Gnomad4 OTH exome AF: 0.000153

GnomAD4 genome AF: 0.000947 AC: 106 AN: 111919 Hom.: 1 Cov.: 23 AF XY: 0.000674 AC XY: 23 AN XY: 34111

Gnomad4 AFR AF: 0.00328

Gnomad4 AMR AF: 0.000376

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000188

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000564 Hom.: 3

Bravo AF: 0.000971

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 14, 2014	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Likely benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Dec 14, 2015	- -

Inborn genetic diseases Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 29, 2017

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

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

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 13, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
Cadd	Benign	0.033
Dann	Benign	0.76

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

Publications

LitVar

Other links and lift over

dbSNP: rs141925310; hg19: chrX-47435578;