Variant rs769924948 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_006950.3(SYN1):c.1367C>T(p.Pro456Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000934 in 1,071,214 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 23)

Exomes 𝑓: 9.3e-7 ( 0 hom. 0 hem. )

Consequence

SYN1
NM_006950.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.41

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06991431).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SYN1	NM_006950.3 linkuse as main transcript	c.1367C>T	p.Pro456Leu	missense_variant	11/13	ENST00000295987.13	NP_008881.2	P17600-1
SYN1	NM_133499.2 linkuse as main transcript	c.1367C>T	p.Pro456Leu	missense_variant	11/13		NP_598006.1	P17600-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SYN1	ENST00000295987.13 linkuse as main transcript	c.1367C>T	p.Pro456Leu	missense_variant	11/13	2	NM_006950.3	ENSP00000295987.7	P17600-1
SYN1	ENST00000340666.5 linkuse as main transcript	c.1367C>T	p.Pro456Leu	missense_variant	11/13	1		ENSP00000343206.4	P17600-2
SYN1	ENST00000640721.1 linkuse as main transcript	c.44C>T	p.Pro15Leu	missense_variant	1/2	5		ENSP00000492857.1	A0A1W2PSE9

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000781

AC:

AN:

127976

Hom.:

AF XY:

0.00

AC XY:

AN XY:

41392

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000473

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

9.34e-7

AC:

AN:

1071214

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

348496

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000334

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000892

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.088

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.57

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.43

T;.;.

FATHMM_MKL

Benign

0.44

LIST_S2

Uncertain

0.88

D;D;T

M_CAP

Benign

0.032

MetaRNN

Benign

0.070

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.34

N;N;.

PrimateAI

Uncertain

0.70

PROVEAN

Uncertain

-2.5

D;D;.

REVEL

Benign

0.029

Sift

Uncertain

0.0040

D;D;.

Sift4G

Uncertain

0.020

D;D;.

Polyphen

0.056

B;B;.

Vest4

0.32

MutPred

0.41

Gain of stability (P = 0.0053);Gain of stability (P = 0.0053);.;

MVP

0.19

MPC

1.0

ClinPred

0.31

GERP RS

4.3

Varity_R

0.14

gMVP

0.20

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over