X-47607150-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_006950.3(SYN1):c.426A>G(p.Lys142Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00113 in 1,209,945 control chromosomes in the GnomAD database, including 6 homozygotes. There are 597 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 0.00067 ( 0 hom., 23 hem., cov: 22)

Exomes 𝑓: 0.0012 ( 6 hom. 574 hem. )

Consequence

SYN1
NM_006950.3 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 2.52

Variant links:

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 links:

ENSG00000283743 (HGNC:):

ENSG00000283743 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.49).

BP6

Variant X-47607150-T-C is Benign according to our data. Variant chrX-47607150-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 207459.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-47607150-T-C is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=2.52 with no splicing effect.

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.000669 (75/112079) while in subpopulation SAS AF = 0.00556 (15/2699). AF 95% confidence interval is 0.00343. There are 0 homozygotes in GnomAd4. There are 23 alleles in the male GnomAd4 subpopulation. Median coverage is 22. This position passed quality control check.

BS2

High Hemizygotes in GnomAd4 at 23 XLR,XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYN1	NM_006950.3 link	c.426A>G	p.Lys142Lys	synonymous_variant	Exon 2 of 13	ENST00000295987.13	NP_008881.2	P17600-1
SYN1	NM_133499.2 link	c.426A>G	p.Lys142Lys	synonymous_variant	Exon 2 of 13		NP_598006.1	P17600-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYN1	ENST00000295987.13 link	c.426A>G	p.Lys142Lys	synonymous_variant	Exon 2 of 13	2	NM_006950.3	ENSP00000295987.7		P17600-1

Frequencies

GnomAD3 genomes

AF:

0.000678

AC:

AN:

112028

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000325

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000190

Gnomad ASJ

AF:

0.00113

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00554

Gnomad FIN

AF:

0.000985

Gnomad MID

AF:

0.00418

Gnomad NFE

AF:

0.000883

Gnomad OTH

AF:

0.000668

GnomAD2 exomes

AF:

0.00122

AC:

224

AN:

183391

AF XY:

0.00189

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000729

Gnomad ASJ exome

AF:

0.000267

Gnomad EAS exome

AF:

0.000144

Gnomad FIN exome

AF:

0.000812

Gnomad NFE exome

AF:

0.000586

Gnomad OTH exome

AF:

0.00132

GnomAD4 exome

AF:

0.00117

AC:

1288

AN:

1097866

Hom.:

Cov.:

AF XY:

0.00158

AC XY:

574

AN XY:

363232

show subpopulations

African (AFR)

AF:

0.000152

AC:

AN:

26394

American (AMR)

AF:

0.000142

AC:

AN:

35200

Ashkenazi Jewish (ASJ)

AF:

0.000361

AC:

AN:

19371

East Asian (EAS)

AF:

0.0000662

AC:

AN:

30191

South Asian (SAS)

AF:

0.00939

AC:

508

AN:

54127

European-Finnish (FIN)

AF:

0.000592

AC:

AN:

40510

Middle Eastern (MID)

AF:

0.00484

AC:

AN:

4134

European-Non Finnish (NFE)

AF:

0.000766

AC:

645

AN:

841858

Other (OTH)

AF:

0.00158

AC:

AN:

46081

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

116

155

194

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.000669

AC:

AN:

112079

Hom.:

Cov.:

AF XY:

0.000671

AC XY:

AN XY:

34259

show subpopulations

African (AFR)

AF:

0.0000324

AC:

AN:

30875

American (AMR)

AF:

0.000189

AC:

AN:

10555

Ashkenazi Jewish (ASJ)

AF:

0.00113

AC:

AN:

2657

East Asian (EAS)

AF:

0.00

AC:

AN:

3575

South Asian (SAS)

AF:

0.00556

AC:

AN:

2699

European-Finnish (FIN)

AF:

0.000985

AC:

AN:

6089

Middle Eastern (MID)

AF:

0.00

AC:

AN:

217

European-Non Finnish (NFE)

AF:

0.000883

AC:

AN:

53210

Other (OTH)

AF:

0.000659

AC:

AN:

1517

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.000491

Hom.:

Bravo

AF:

0.000434

EpiCase

AF:

0.000872

EpiControl

AF:

0.000771

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Jun 05, 2018

Genetic Services Laboratory, University of Chicago

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

May 20, 2015

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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. -

not provided

Benign:2

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

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

Benign:1

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

History of neurodevelopmental disorder

Benign:1

May 31, 2016

Ambry Genetics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Synonymous alterations with insufficient evidence to classify as benign -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.49

CADD

Benign

(source)

DANN

Benign

0.68

PhyloP100

2.5

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.12

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

Below is the list of publications found by LitVar for variant X:47607150 T>C . It may be empty.

X-47607150-T-C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over