rs762716551

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_001242394.2(SYTL3):c.109C>T(p.Arg37Trp) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000211 in 1,613,100 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000018 ( 0 hom. )

Consequence

SYTL3
NM_001242394.2 missense, splice_region

Scores

Splicing: ADA: 0.6383

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.89

Publications

1 publications found

Variant links:

Genes affected

SYTL3 (HGNC:15587): (synaptotagmin like 3) The protein encoded by this gene belongs to a family of peripheral membrane proteins that play a role in vesicular trafficking. This protein binds phospholipids in the presence of calcium ions. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2016]

SYTL3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.31117192).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYTL3	NM_001242394.2 link	c.109C>T	p.Arg37Trp	missense_variant, splice_region_variant	Exon 4 of 18	ENST00000611299.5	NP_001229323.1	Q4VX76-1B4E2A9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SYTL3	ENST00000611299.5 link	c.109C>T	p.Arg37Trp	missense_variant, splice_region_variant	Exon 4 of 18	5	NM_001242394.2	ENSP00000483936.1	Q4VX76-1
SYTL3	ENST00000360448.8 link	c.109C>T	p.Arg37Trp	missense_variant, splice_region_variant	Exon 5 of 19	5		ENSP00000353631.4	Q4VX76-1
SYTL3	ENST00000367081.7 link	c.109C>T	p.Arg37Trp	missense_variant, splice_region_variant	Exon 4 of 16	5		ENSP00000356048.4	Q4VX76-2

Frequencies

GnomAD3 genomes

AF:

0.0000526

AC:

AN:

152042

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000197

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.000479

GnomAD2 exomes

AF:

0.0000239

AC:

AN:

250848

AF XY:

0.0000221

show subpopulations

Gnomad AFR exome

AF:

0.0000617

Gnomad AMR exome

AF:

0.0000871

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000178

AC:

AN:

1461058

Hom.:

Cov.:

AF XY:

0.0000193

AC XY:

AN XY:

726816

show subpopulations

African (AFR)

AF:

0.000149

AC:

AN:

33450

American (AMR)

AF:

0.000112

AC:

AN:

44696

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26126

East Asian (EAS)

AF:

0.00

AC:

AN:

39674

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86202

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53400

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5326

European-Non Finnish (NFE)

AF:

0.0000108

AC:

AN:

1111878

Other (OTH)

AF:

0.0000497

AC:

AN:

60306

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000526

AC:

AN:

152042

Hom.:

Cov.:

AF XY:

0.0000673

AC XY:

AN XY:

74278

show subpopulations

African (AFR)

AF:

0.0000242

AC:

AN:

41400

American (AMR)

AF:

0.000197

AC:

AN:

15260

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5158

South Asian (SAS)

AF:

0.000207

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10606

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68018

Other (OTH)

AF:

0.000479

AC:

AN:

2086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.431

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.000121

ExAC

AF:

0.0000247

AC:

EpiCase

AF:

0.0000546

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

Dec 18, 2023

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.109C>T (p.R37W) alteration is located in exon 4 (coding exon 1) of the SYTL3 gene. This alteration results from a C to T substitution at nucleotide position 109, causing the arginine (R) at amino acid position 37 to be replaced by a tryptophan (W). 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

Uncertain

0.039

BayesDel_noAF

Uncertain

0.020

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.59

.;D;D;D

Eigen

Benign

0.016

Eigen_PC

Benign

0.067

FATHMM_MKL

Benign

0.58

LIST_S2

Uncertain

0.86

D;.;D;.

M_CAP

Uncertain

0.11

MetaRNN

Benign

0.31

T;T;T;T

MetaSVM

Uncertain

-0.27

MutationAssessor

Pathogenic

3.3

M;M;M;M

PhyloP100

1.9

PrimateAI

Benign

0.41

PROVEAN

Pathogenic

-6.3

.;D;.;D

REVEL

Uncertain

0.49

Sift

Pathogenic

0.0

.;D;.;D

Sift4G

Uncertain

0.021

D;D;D;D

Polyphen

0.094

B;B;B;B

Vest4

0.43

MutPred

0.40

Loss of disorder (P = 0.0121);Loss of disorder (P = 0.0121);Loss of disorder (P = 0.0121);Loss of disorder (P = 0.0121);

MVP

0.64

MPC

0.017

ClinPred

0.91

GERP RS

3.4

Varity_R

0.41

gMVP

0.55

Mutation Taster

=39/61

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.64

dbscSNV1_RF

Benign

0.40

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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rs762716551

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over