6-158763446-G-C

Variant summary

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

The NM_001242394.2(SYTL3):​c.1660G>C​(p.Val554Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,856 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. V554F) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

SYTL3
NM_001242394.2 missense

Scores

1
8
10

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.25

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]

Genome browser will be placed here

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
SYTL3NM_001242394.2 linkc.1660G>C p.Val554Leu missense_variant Exon 17 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.1660G>C p.Val554Leu missense_variant Exon 17 of 18 5 NM_001242394.2 ENSP00000483936.1 Q4VX76-1
SYTL3ENST00000360448.8 linkc.1660G>C p.Val554Leu missense_variant Exon 18 of 19 5 ENSP00000353631.4 Q4VX76-1
SYTL3ENST00000367081.7 linkc.1456G>C p.Val486Leu missense_variant Exon 15 of 16 5 ENSP00000356048.4 Q4VX76-2

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD2 exomes
AF:
0.00000398
AC:
1
AN:
251494
AF XY:
0.00000736
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 FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000879
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461856
Hom.:
0
Cov.:
34
AF XY:
0.00000138
AC XY:
1
AN XY:
727238
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
0.00
AC:
0
AN:
33480
American (AMR)
AF:
0.00
AC:
0
AN:
44720
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26136
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39700
South Asian (SAS)
AF:
0.00
AC:
0
AN:
86258
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53420
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5762
European-Non Finnish (NFE)
AF:
8.99e-7
AC:
1
AN:
1111988
Other (OTH)
AF:
0.00
AC:
0
AN:
60392
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.325
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.25
BayesDel_addAF
Pathogenic
0.20
D
BayesDel_noAF
Uncertain
0.050
CADD
Benign
17
DANN
Uncertain
0.99
DEOGEN2
Benign
0.072
.;T;T;T
Eigen
Benign
-0.091
Eigen_PC
Benign
-0.14
FATHMM_MKL
Benign
0.58
D
LIST_S2
Benign
0.78
T;.;T;.
M_CAP
Benign
0.052
D
MetaRNN
Uncertain
0.54
D;D;D;D
MetaSVM
Benign
-0.47
T
MutationAssessor
Uncertain
2.3
.;M;M;M
PhyloP100
2.3
PrimateAI
Uncertain
0.58
T
PROVEAN
Benign
-1.7
.;.;.;N
REVEL
Uncertain
0.59
Sift
Uncertain
0.0050
.;.;.;D
Sift4G
Uncertain
0.0080
D;D;D;D
Polyphen
0.83
P;B;B;B
Vest4
0.52
MutPred
0.71
.;Gain of sheet (P = 0.1945);Gain of sheet (P = 0.1945);Gain of sheet (P = 0.1945);
MVP
0.46
MPC
0.028
ClinPred
0.76
D
GERP RS
3.2
Varity_R
0.19
gMVP
0.40
Mutation Taster
=85/15
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: rs774693205; hg19: chr6-159184478; API