Genetic Variant NM_006950.3:c.1621G>C (chrX-47574363-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_006950.3(SYN1):c.1621G>C(p.Gly541Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 23)

Exomes 𝑓: 0.0 ( 0 hom. 0 hem. )

Failed GnomAD Quality Control

Consequence

SYN1
NM_006950.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.90

Publications

0 publications found

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 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

SYN1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.14138553).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYN1	NM_006950.3 link	c.1621G>C	p.Gly541Arg	missense_variant	Exon 12 of 13	ENST00000295987.13	NP_008881.2	P17600-1
SYN1	NM_133499.2 link	c.1621G>C	p.Gly541Arg	missense_variant	Exon 12 of 13		NP_598006.1	P17600-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SYN1	ENST00000295987.13 link	c.1621G>C	p.Gly541Arg	missense_variant	Exon 12 of 13	2	NM_006950.3	ENSP00000295987.7	P17600-1
SYN1	ENST00000340666.5 link	c.1621G>C	p.Gly541Arg	missense_variant	Exon 12 of 13	1		ENSP00000343206.4	P17600-2
SYN1	ENST00000640721.1 link	c.70+325G>C		intron_variant	Intron 1 of 1	5		ENSP00000492857.1	A0A1W2PSE9

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

912155

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

284483

African (AFR)

AF:

0.00

AC:

AN:

18852

American (AMR)

AF:

0.00

AC:

AN:

9048

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

12494

East Asian (EAS)

AF:

0.00

AC:

AN:

21236

South Asian (SAS)

AF:

0.00

AC:

AN:

30277

European-Finnish (FIN)

AF:

0.00

AC:

AN:

22085

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2396

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

757600

Other (OTH)

AF:

0.00

AC:

AN:

38167

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Sep 10, 2013

Genetic Services Laboratory, University of Chicago

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.36

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.63

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.18

T;.

FATHMM_MKL

Benign

0.18

LIST_S2

Benign

0.84

T;T

M_CAP

Uncertain

0.24

MetaRNN

Benign

0.14

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.55

N;N

PhyloP100

1.9

PrimateAI

Pathogenic

0.92

PROVEAN

Benign

-0.15

N;N

REVEL

Benign

0.067

Sift

Benign

0.15

T;D

Sift4G

Benign

0.19

T;T

Polyphen

0.0050

B;B

Vest4

0.35

MutPred

0.41

Gain of methylation at G541 (P = 0.0085);Gain of methylation at G541 (P = 0.0085);

MVP

0.22

MPC

3.4

ClinPred

0.43

GERP RS

3.1

PromoterAI

-0.023

Neutral

(source)

Varity_R

0.063

gMVP

0.31

Mutation Taster

=88/12

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over