chr11-85698040-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_206927.4(SYTL2):​c.6307G>A​(p.Val2103Met) variant causes a missense change. The variant allele was found at a frequency of 0.00000372 in 1,613,700 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. V2103L) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

SYTL2
NM_206927.4 missense

Scores

7
8
4

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.69
Variant links:
Genes affected
SYTL2 (HGNC:15585): (synaptotagmin like 2) The protein encoded by this gene is a synaptotagmin-like protein (SLP) that belongs to a C2 domain-containing protein family. The SLP homology domain (SHD) of this protein has been shown to specifically bind the GTP-bound form of Ras-related protein Rab-27A (RAB27A). This protein plays a role in RAB27A-dependent vesicle trafficking and controls melanosome distribution in the cell periphery. Alternative splicing results in multiple transcript variants encoding distinct isoforms.[provided by RefSeq, Jun 2009]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 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
SYTL2NM_206927.4 linkc.6307G>A p.Val2103Met missense_variant Exon 18 of 20 ENST00000359152.10 NP_996810.2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SYTL2ENST00000359152.10 linkc.6307G>A p.Val2103Met missense_variant Exon 18 of 20 1 NM_206927.4 ENSP00000352065.7 A0A8J9FM55

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152122
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000724
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
GnomAD3 exomes
AF:
0.00000796
AC:
2
AN:
251212
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135786
show subpopulations
Gnomad AFR exome
AF:
0.0000615
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000880
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000205
AC:
3
AN:
1461578
Hom.:
0
Cov.:
30
AF XY:
0.00000413
AC XY:
3
AN XY:
727112
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.0000383
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000180
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152122
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74306
show subpopulations
Gnomad4 AFR
AF:
0.0000724
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000370
Hom.:
0
Bravo
AF:
0.0000113
ExAC
AF:
0.00000824
AC:
1
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.60
BayesDel_addAF
Uncertain
0.089
D
BayesDel_noAF
Uncertain
0.070
CADD
Pathogenic
27
DANN
Uncertain
1.0
DEOGEN2
Benign
0.26
.;.;.;.;.;.;.;T;D;.;.;.;.
Eigen
Pathogenic
0.85
Eigen_PC
Pathogenic
0.82
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Pathogenic
1.0
D;D;D;.;.;D;D;D;D;D;D;D;.
M_CAP
Benign
0.034
D
MetaRNN
Uncertain
0.61
D;D;D;D;D;D;D;D;D;D;D;D;D
MetaSVM
Benign
-0.88
T
MutationAssessor
Pathogenic
3.7
.;.;.;.;.;.;.;.;H;.;.;.;.
PrimateAI
Uncertain
0.57
T
PROVEAN
Uncertain
-2.4
.;N;.;N;D;D;D;.;N;D;N;.;N
REVEL
Uncertain
0.31
Sift
Pathogenic
0.0
.;D;.;D;D;D;D;.;D;D;D;.;D
Sift4G
Uncertain
0.0040
D;D;D;D;D;D;D;D;D;D;D;D;D
Polyphen
1.0
D;D;.;D;.;.;D;.;D;D;D;.;D
Vest4
0.80
MVP
0.54
MPC
0.094
ClinPred
0.98
D
GERP RS
5.8
Varity_R
0.45
gMVP
0.62

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs147226965; hg19: chr11-85409083; API