6-158718144-C-G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001242394.2(SYTL3):​c.653C>G​(p.Pro218Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000717 in 1,394,426 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P218L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 7.2e-7 ( 0 hom. )

Consequence

SYTL3
NM_001242394.2 missense

Scores

1
18

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.10

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]

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.11031073).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SYTL3NM_001242394.2 linkc.653C>G p.Pro218Arg missense_variant Exon 10 of 18 ENST00000611299.5 NP_001229323.1 Q4VX76-1B4E2A9

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SYTL3ENST00000611299.5 linkc.653C>G p.Pro218Arg missense_variant Exon 10 of 18 5 NM_001242394.2 ENSP00000483936.1 Q4VX76-1
SYTL3ENST00000360448.8 linkc.653C>G p.Pro218Arg missense_variant Exon 11 of 19 5 ENSP00000353631.4 Q4VX76-1
SYTL3ENST00000367081.7 linkc.517-7359C>G intron_variant Intron 8 of 15 5 ENSP00000356048.4 Q4VX76-2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
7.17e-7
AC:
1
AN:
1394426
Hom.:
0
Cov.:
30
AF XY:
0.00
AC XY:
0
AN XY:
687786
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
31392
American (AMR)
AF:
0.00
AC:
0
AN:
35330
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
25108
East Asian (EAS)
AF:
0.00
AC:
0
AN:
35290
South Asian (SAS)
AF:
0.00
AC:
0
AN:
78630
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
48088
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5682
European-Non Finnish (NFE)
AF:
9.28e-7
AC:
1
AN:
1077066
Other (OTH)
AF:
0.00
AC:
0
AN:
57840
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.425
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.076
BayesDel_addAF
Benign
-0.20
T
BayesDel_noAF
Benign
-0.52
CADD
Benign
6.7
DANN
Benign
0.91
DEOGEN2
Benign
0.0067
T;T;T
Eigen
Benign
-0.67
Eigen_PC
Benign
-0.70
FATHMM_MKL
Benign
0.11
N
LIST_S2
Benign
0.72
.;T;.
M_CAP
Benign
0.0048
T
MetaRNN
Benign
0.11
T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Uncertain
2.4
M;M;M
PhyloP100
2.1
PrimateAI
Benign
0.28
T
PROVEAN
Benign
-1.9
.;.;N
REVEL
Benign
0.035
Sift
Benign
0.046
.;.;D
Sift4G
Benign
0.43
T;T;T
Polyphen
0.040
B;B;B
Vest4
0.15
MutPred
0.33
Gain of MoRF binding (P = 0.0115);Gain of MoRF binding (P = 0.0115);Gain of MoRF binding (P = 0.0115);
MVP
0.28
MPC
0.019
ClinPred
0.098
T
GERP RS
2.9
Varity_R
0.046
gMVP
0.35
Mutation Taster
=96/4
polymorphism

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

Other links and lift over

dbSNP: rs569809355; hg19: chr6-159139176; API