Variant 19-50625412-C-A 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_001160329.2(SYT3):c.1555G>T(p.Ala519Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000116 in 1,554,704 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000078 ( 0 hom. )

Consequence

SYT3
NM_001160329.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.837

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:

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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=0.14131695).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SYT3	NM_001160329.2 link	c.1555G>T	p.Ala519Ser	missense_variant	8/11	ENST00000600079.6	NP_001153801.1	Q9BQG1A0A024R4I9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SYT3	ENST00000600079.6 link	c.1555G>T	p.Ala519Ser	missense_variant	8/11	1	NM_001160329.2	ENSP00000469398.1	Q9BQG1
SYT3	ENST00000338916.8 link	c.1555G>T	p.Ala519Ser	missense_variant	6/9	1		ENSP00000340914.3	Q9BQG1
SYT3	ENST00000593901.5 link	c.1555G>T	p.Ala519Ser	missense_variant	8/11	1		ENSP00000468982.1	Q9BQG1
SYT3	ENST00000595117.1 link	n.391G>T		non_coding_transcript_exon_variant	2/5	2

Frequencies

GnomAD3 genomes

AF:

0.0000462

AC:

AN:

151596

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000970

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000196

Gnomad SAS

AF:

0.000418

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000125

AC:

AN:

160380

Hom.:

AF XY:

0.0000118

AC XY:

AN XY:

84894

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000400

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000430

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000784

AC:

AN:

1402990

Hom.:

Cov.:

AF XY:

0.00000578

AC XY:

AN XY:

692532

show subpopulations

Gnomad4 AFR exome

AF:

0.0000627

Gnomad4 AMR exome

AF:

0.0000278

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000276

Gnomad4 SAS exome

AF:

0.0000502

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000516

GnomAD4 genome

AF:

0.0000461

AC:

AN:

151714

Hom.:

Cov.:

AF XY:

0.0000540

AC XY:

AN XY:

74120

show subpopulations

Gnomad4 AFR

AF:

0.0000967

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000196

Gnomad4 SAS

AF:

0.000419

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000658

Hom.:

Bravo

AF:

0.0000340

ExAC

AF:

0.00000871

AC:

Asia WGS

AF:

0.00115

AC:

AN:

3478

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

Mar 01, 2023

The c.1555G>T (p.A519S) alteration is located in exon 6 (coding exon 6) of the SYT3 gene. This alteration results from a G to T substitution at nucleotide position 1555, causing the alanine (A) at amino acid position 519 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

0.17

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.33

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.055

T;T;T

Eigen

Benign

-0.50

Eigen_PC

Benign

-0.36

FATHMM_MKL

Uncertain

0.76

LIST_S2

Benign

0.84

.;.;T

M_CAP

Benign

0.036

MetaRNN

Benign

0.14

T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

-0.66

N;N;N

PrimateAI

Uncertain

0.72

PROVEAN

Benign

-0.75

N;.;.

REVEL

Benign

0.12

Sift

Benign

0.52

T;.;.

Sift4G

Benign

0.61

T;T;T

Polyphen

0.27

B;B;B

Vest4

0.33

MVP

0.50

MPC

0.69

ClinPred

0.25

GERP RS

3.5

Varity_R

0.075

gMVP

0.43

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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