Variant 19-50629984-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001160329.2(SYT3):c.862G>A(p.Gly288Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000156 in 1,613,612 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000072 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00016 ( 0 hom. )

Consequence

SYT3
NM_001160329.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.54

Variant links:

Genes affected

SYT3 (HGNC:11511): (synaptotagmin 3) Predicted to enable several functions, including phospholipid binding activity; protein dimerization activity; and syntaxin binding activity. Involved in positive regulation of dendrite extension. Located in endosome. [provided by Alliance of Genome Resources, Apr 2022]

SYT3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.042450517).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SYT3	NM_001160329.2 link	c.862G>A	p.Gly288Ser	missense_variant	5/11	ENST00000600079.6	NP_001153801.1	Q9BQG1A0A024R4I9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SYT3	ENST00000600079.6 link	c.862G>A	p.Gly288Ser	missense_variant	5/11	1	NM_001160329.2	ENSP00000469398.1	Q9BQG1
SYT3	ENST00000338916.8 link	c.862G>A	p.Gly288Ser	missense_variant	3/9	1		ENSP00000340914.3	Q9BQG1
SYT3	ENST00000593901.5 link	c.862G>A	p.Gly288Ser	missense_variant	5/11	1		ENSP00000468982.1	Q9BQG1

Frequencies

GnomAD3 genomes

AF:

0.0000723

AC:

AN:

152096

Hom.:

Cov.:

show subpopulations

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:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000162

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000799

AC:

AN:

250442

Hom.:

AF XY:

0.0000665

AC XY:

AN XY:

135358

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000290

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:

0.000159

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.000165

AC:

241

AN:

1461516

Hom.:

Cov.:

AF XY:

0.000182

AC XY:

132

AN XY:

727048

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000750

Gnomad4 NFE exome

AF:

0.000207

Gnomad4 OTH exome

AF:

0.0000994

GnomAD4 genome

AF:

0.0000723

AC:

AN:

152096

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74286

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000162

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000387

Hom.:

Bravo

AF:

0.0000945

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000115

AC:

EpiCase

AF:

0.000273

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 21, 2022

The c.862G>A (p.G288S) alteration is located in exon 3 (coding exon 3) of the SYT3 gene. This alteration results from a G to A substitution at nucleotide position 862, causing the glycine (G) at amino acid position 288 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.073

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Benign

0.16

DEOGEN2

Benign

0.020

T;T;T

Eigen

Benign

-0.66

Eigen_PC

Benign

-0.57

FATHMM_MKL

Benign

0.71

LIST_S2

Benign

0.37

.;.;T

M_CAP

Benign

0.011

MetaRNN

Benign

0.042

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

N;N;N

PrimateAI

Uncertain

0.60

PROVEAN

Benign

0.85

N;.;.

REVEL

Benign

0.044

Sift

Benign

0.97

T;.;.

Sift4G

Benign

0.92

T;T;T

Polyphen

0.0080

B;B;B

Vest4

0.21

MVP

0.55

MPC

0.50

ClinPred

0.14

GERP RS

3.3

Varity_R

0.066

gMVP

0.15

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over