19-55174522-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_003180.3(SYT5):​c.955G>A​(p.Val319Ile) variant causes a missense change. The variant allele was found at a frequency of 0.0000743 in 1,614,002 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000068 ( 0 hom. )

Consequence

SYT5
NM_003180.3 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.11
Variant links:
Genes affected
SYT5 (HGNC:11513): (synaptotagmin 5) Synaptotagmins, such as SYT5, are a family of type III membrane proteins characterized by cytoplasmic repeats related to protein kinase C (see MIM 176960) regulatory (C2) domains, which are thought to bind calcium. Synaptotagmins may act both as negative regulators of vesicle fusion, allowing fusion in the presence of calcium, and as calcium receptors or sensor molecules (summary by Hudson and Birnbaum, 1995 [PubMed 7597049]).[supplied by OMIM, Feb 2011]
DNAAF3-AS1 (HGNC:55292): (DNAAF3 antisense RNA 1)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.020932257).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SYT5NM_003180.3 linkc.955G>A p.Val319Ile missense_variant Exon 8 of 9 ENST00000354308.8 NP_003171.2 O00445-1A0A024R4N8

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SYT5ENST00000354308.8 linkc.955G>A p.Val319Ile missense_variant Exon 8 of 9 1 NM_003180.3 ENSP00000346265.2 O00445-1

Frequencies

GnomAD3 genomes
AF:
0.000131
AC:
20
AN:
152162
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.000576
Gnomad EAS
AF:
0.00173
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000882
Gnomad OTH
AF:
0.000957
GnomAD3 exomes
AF:
0.000135
AC:
34
AN:
251274
Hom.:
0
AF XY:
0.000133
AC XY:
18
AN XY:
135814
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.000994
Gnomad EAS exome
AF:
0.000381
Gnomad SAS exome
AF:
0.000196
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000792
Gnomad OTH exome
AF:
0.000326
GnomAD4 exome
AF:
0.0000684
AC:
100
AN:
1461722
Hom.:
0
Cov.:
31
AF XY:
0.0000674
AC XY:
49
AN XY:
727184
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00111
Gnomad4 EAS exome
AF:
0.000605
Gnomad4 SAS exome
AF:
0.000139
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000207
Gnomad4 OTH exome
AF:
0.000182
GnomAD4 genome
AF:
0.000131
AC:
20
AN:
152280
Hom.:
0
Cov.:
32
AF XY:
0.000175
AC XY:
13
AN XY:
74450
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.000576
Gnomad4 EAS
AF:
0.00174
Gnomad4 SAS
AF:
0.000208
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000882
Gnomad4 OTH
AF:
0.000947
Alfa
AF:
0.000131
Hom.:
0
Bravo
AF:
0.0000982
ExAC
AF:
0.0000988
AC:
12
Asia WGS
AF:
0.00260
AC:
10
AN:
3478
EpiCase
AF:
0.0000545
EpiControl
AF:
0.0000593

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Dec 14, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.955G>A (p.V319I) alteration is located in exon 8 (coding exon 7) of the SYT5 gene. This alteration results from a G to A substitution at nucleotide position 955, causing the valine (V) at amino acid position 319 to be replaced by an isoleucine (I). 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
0.094
BayesDel_addAF
Benign
-0.37
T
BayesDel_noAF
Benign
-0.45
CADD
Benign
23
DANN
Benign
0.94
DEOGEN2
Benign
0.087
.;T;T;T
Eigen
Benign
-0.51
Eigen_PC
Benign
-0.30
FATHMM_MKL
Benign
0.71
D
LIST_S2
Uncertain
0.87
D;.;T;D
M_CAP
Benign
0.0053
T
MetaRNN
Benign
0.021
T;T;T;T
MetaSVM
Benign
-0.95
T
MutationAssessor
Benign
-0.56
.;N;N;.
PrimateAI
Uncertain
0.49
T
PROVEAN
Benign
0.70
.;N;N;.
REVEL
Benign
0.093
Sift
Benign
1.0
.;T;T;.
Sift4G
Benign
1.0
T;T;T;T
Polyphen
0.0010
.;B;B;.
Vest4
0.16
MVP
0.59
MPC
0.53
ClinPred
0.075
T
GERP RS
3.4
Varity_R
0.046
gMVP
0.11

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: rs550607880; hg19: chr19-55685890; API