6-158718126-A-T

Variant summary

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

The NM_001242394.2(SYTL3):​c.635A>T​(p.His212Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000287 in 1,394,492 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. H212R) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000029 ( 0 hom. )

Consequence

SYTL3
NM_001242394.2 missense

Scores

1
18

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.40

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=0.07382941).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SYTL3NM_001242394.2 linkc.635A>T p.His212Leu 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.635A>T p.His212Leu missense_variant Exon 10 of 18 5 NM_001242394.2 ENSP00000483936.1 Q4VX76-1
SYTL3ENST00000360448.8 linkc.635A>T p.His212Leu missense_variant Exon 11 of 19 5 ENSP00000353631.4 Q4VX76-1
SYTL3ENST00000367081.7 linkc.517-7377A>T intron_variant Intron 8 of 15 5 ENSP00000356048.4 Q4VX76-2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000287
AC:
4
AN:
1394492
Hom.:
0
Cov.:
30
AF XY:
0.00000291
AC XY:
2
AN XY:
687766
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
31394
American (AMR)
AF:
0.00
AC:
0
AN:
35288
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
25074
East Asian (EAS)
AF:
0.00
AC:
0
AN:
35346
South Asian (SAS)
AF:
0.0000382
AC:
3
AN:
78634
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
48088
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5678
European-Non Finnish (NFE)
AF:
9.28e-7
AC:
1
AN:
1077150
Other (OTH)
AF:
0.00
AC:
0
AN:
57840
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.413
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.088
BayesDel_addAF
Benign
-0.21
T
BayesDel_noAF
Benign
-0.54
CADD
Benign
5.6
DANN
Benign
0.92
DEOGEN2
Benign
0.0092
T;T;T
Eigen
Benign
-0.69
Eigen_PC
Benign
-0.64
FATHMM_MKL
Benign
0.21
N
LIST_S2
Benign
0.54
.;T;.
M_CAP
Benign
0.0053
T
MetaRNN
Benign
0.074
T;T;T
MetaSVM
Benign
-0.96
T
MutationAssessor
Benign
1.7
L;L;L
PhyloP100
1.4
PrimateAI
Benign
0.30
T
PROVEAN
Uncertain
-2.9
.;.;D
REVEL
Benign
0.024
Sift
Benign
0.38
.;.;T
Sift4G
Benign
0.32
T;T;T
Polyphen
0.0
B;B;B
Vest4
0.19
MutPred
0.32
Gain of stability (P = 0.1152);Gain of stability (P = 0.1152);Gain of stability (P = 0.1152);
MVP
0.26
MPC
0.018
ClinPred
0.079
T
GERP RS
1.4
Varity_R
0.090
gMVP
0.32
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: rs751194317; hg19: chr6-159139158; API