Variant 19-50632361-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001160329.2(SYT3):c.599T>A(p.Leu200Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000011 in 1,457,554 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

SYT3
NM_001160329.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.43

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 Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SYT3	NM_001160329.2 link	c.599T>A	p.Leu200Gln	missense_variant	4/11	ENST00000600079.6	NP_001153801.1	Q9BQG1A0A024R4I9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SYT3	ENST00000600079.6 link	c.599T>A	p.Leu200Gln	missense_variant	4/11	1	NM_001160329.2	ENSP00000469398.1	Q9BQG1
SYT3	ENST00000338916.8 link	c.599T>A	p.Leu200Gln	missense_variant	2/9	1		ENSP00000340914.3	Q9BQG1
SYT3	ENST00000593901.5 link	c.599T>A	p.Leu200Gln	missense_variant	4/11	1		ENSP00000468982.1	Q9BQG1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000399

AC:

AN:

250760

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135572

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.00000883

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000110

AC:

AN:

1457554

Hom.:

Cov.:

AF XY:

0.0000110

AC XY:

AN XY:

724102

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

0.0000144

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000824

AC:

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 18, 2023

The c.599T>A (p.L200Q) alteration is located in exon 2 (coding exon 2) of the SYT3 gene. This alteration results from a T to A substitution at nucleotide position 599, causing the leucine (L) at amino acid position 200 to be replaced by a glutamine (Q). 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

0.13

BayesDel_addAF

Benign

-0.019

BayesDel_noAF

Benign

-0.27

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.033

T;T;T

Eigen

Uncertain

0.31

Eigen_PC

Uncertain

0.39

FATHMM_MKL

Uncertain

0.81

LIST_S2

Benign

0.77

.;.;T

M_CAP

Benign

0.019

MetaRNN

Uncertain

0.45

T;T;T

MetaSVM

Benign

-0.84

MutationAssessor

Benign

0.90

L;L;L

PrimateAI

Uncertain

0.65

PROVEAN

Benign

1.9

N;.;.

REVEL

Benign

0.17

Sift

Benign

0.35

T;.;.

Sift4G

Benign

0.34

T;T;T

Polyphen

0.99

D;D;D

Vest4

0.53

MutPred

0.42

Loss of catalytic residue at L200 (P = 0.0022);Loss of catalytic residue at L200 (P = 0.0022);Loss of catalytic residue at L200 (P = 0.0022);

MVP

0.72

MPC

0.51

ClinPred

0.73

GERP RS

5.2

Varity_R

0.21

gMVP

0.53

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