Genetic Variant SYTL3:p.Arg92Gln (chr6-158665559-G-A) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3

The NM_001242394.2(SYTL3):c.275G>A(p.Arg92Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000885 in 1,581,598 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000063 ( 0 hom. )

Consequence

SYTL3
NM_001242394.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.25

Publications

0 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 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.812

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYTL3	NM_001242394.2 link	c.275G>A	p.Arg92Gln	missense_variant	Exon 5 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.275G>A	p.Arg92Gln	missense_variant	Exon 5 of 18	5	NM_001242394.2	ENSP00000483936.1	Q4VX76-1
SYTL3	ENST00000360448.8 link	c.275G>A	p.Arg92Gln	missense_variant	Exon 6 of 19	5		ENSP00000353631.4	Q4VX76-1
SYTL3	ENST00000367081.7 link	c.275G>A	p.Arg92Gln	missense_variant	Exon 5 of 16	5		ENSP00000356048.4	Q4VX76-2

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152174

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000154

AC:

AN:

194424

AF XY:

0.00000963

show subpopulations

Gnomad AFR exome

AF:

0.000163

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000119

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000630

AC:

AN:

1429424

Hom.:

Cov.:

AF XY:

0.00000848

AC XY:

AN XY:

707566

show subpopulations

African (AFR)

AF:

0.0000903

AC:

AN:

33214

American (AMR)

AF:

0.00

AC:

AN:

38022

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25330

East Asian (EAS)

AF:

0.00

AC:

AN:

38622

South Asian (SAS)

AF:

0.00

AC:

AN:

81518

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51174

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5642

European-Non Finnish (NFE)

AF:

0.00000456

AC:

AN:

1096650

Other (OTH)

AF:

0.0000169

AC:

AN:

59252

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000329

AC:

AN:

152174

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74330

show subpopulations

African (AFR)

AF:

0.000121

AC:

AN:

41444

American (AMR)

AF:

0.00

AC:

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68032

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000378

ExAC

AF:

0.0000251

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Apr 15, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.275G>A (p.R92Q) alteration is located in exon 5 (coding exon 2) of the SYTL3 gene. This alteration results from a G to A substitution at nucleotide position 275, causing the arginine (R) at amino acid position 92 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

0.11

BayesDel_addAF

Benign

-0.0027

BayesDel_noAF

Benign

-0.24

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.37

.;T;T;T

Eigen

Uncertain

0.43

Eigen_PC

Uncertain

0.38

FATHMM_MKL

Uncertain

0.89

LIST_S2

Uncertain

0.86

D;.;D;.

M_CAP

Uncertain

0.099

MetaRNN

Pathogenic

0.81

D;D;D;D

MetaSVM

Uncertain

-0.14

MutationAssessor

Uncertain

2.5

M;M;M;M

PhyloP100

6.3

PrimateAI

Uncertain

0.59

PROVEAN

Uncertain

-3.4

.;D;.;D

REVEL

Uncertain

0.56

Sift

Benign

0.049

.;D;.;T

Sift4G

Benign

0.092

T;T;T;T

Polyphen

0.99

D;D;D;D

Vest4

0.47

MutPred

0.87

Loss of MoRF binding (P = 0.0121);Loss of MoRF binding (P = 0.0121);Loss of MoRF binding (P = 0.0121);Loss of MoRF binding (P = 0.0121);

MVP

0.58

MPC

0.10

ClinPred

0.89

GERP RS

5.8

Varity_R

0.21

gMVP

0.48

Mutation Taster

=273/27

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

6-158665559-G-A

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