Genetic Variant SYTL3:p.Gln204Arg (chr6-158718102-A-G) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001242394.2(SYTL3):c.611A>G(p.Gln204Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000072 in 1,389,808 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.2e-7 ( 0 hom. )

Consequence

SYTL3
NM_001242394.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.30

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYTL3	NM_001242394.2 link	c.611A>G	p.Gln204Arg	missense_variant	Exon 10 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.611A>G	p.Gln204Arg	missense_variant	Exon 10 of 18	5	NM_001242394.2	ENSP00000483936.1	Q4VX76-1
SYTL3	ENST00000360448.8 link	c.611A>G	p.Gln204Arg	missense_variant	Exon 11 of 19	5		ENSP00000353631.4	Q4VX76-1
SYTL3	ENST00000367081.7 link	c.517-7401A>G		intron_variant	Intron 8 of 15	5		ENSP00000356048.4	Q4VX76-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.20e-7

AC:

AN:

1389808

Hom.:

Cov.:

AF XY:

0.00000146

AC XY:

AN XY:

685526

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31128

American (AMR)

AF:

0.00

AC:

AN:

34508

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24806

East Asian (EAS)

AF:

0.00

AC:

AN:

35162

South Asian (SAS)

AF:

0.00

AC:

AN:

77976

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47824

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5652

European-Non Finnish (NFE)

AF:

9.30e-7

AC:

AN:

1075130

Other (OTH)

AF:

0.00

AC:

AN:

57622

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jul 30, 2023

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.611A>G (p.Q204R) alteration is located in exon 10 (coding exon 7) of the SYTL3 gene. This alteration results from a A to G substitution at nucleotide position 611, causing the glutamine (Q) at amino acid position 204 to be replaced by an arginine (R). 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

0.15

BayesDel_addAF

Benign

-0.042

BayesDel_noAF

Benign

-0.30

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0056

T;T;T

Eigen

Uncertain

0.55

Eigen_PC

Uncertain

0.54

FATHMM_MKL

Uncertain

0.84

LIST_S2

Benign

0.77

.;T;.

M_CAP

Benign

0.012

MetaRNN

Benign

0.27

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.7

M;M;M

PhyloP100

5.3

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-2.0

.;.;N

REVEL

Benign

0.13

Sift

Benign

0.19

.;.;T

Sift4G

Benign

0.34

T;T;T

Polyphen

1.0

D;D;D

Vest4

0.31

MutPred

0.23

Gain of MoRF binding (P = 0.0217);Gain of MoRF binding (P = 0.0217);Gain of MoRF binding (P = 0.0217);

MVP

0.32

MPC

0.14

ClinPred

0.93

GERP RS

5.2

Varity_R

0.17

gMVP

0.44

Mutation Taster

=58/42

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.22

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.22

Position offset: -15

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over