10-46580325-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_031912.5(SYT15):​c.169C>T​(p.Arg57Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 7/11 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000098 ( 0 hom., cov: 13)
Exomes 𝑓: 0.0000091 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

SYT15
NM_031912.5 missense

Scores

3
6

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.32
Variant links:
Genes affected
SYT15 (HGNC:17167): (synaptotagmin 15) This gene encodes a member of the Synaptotagmin (Syt) family of membrane trafficking proteins. Members of this family contain a transmembrane region and a C-terminal-type tandem C2 domain. Unlike related family members, the encoded protein may be involved in membrane trafficking in non-neuronal tissues. Two trancript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.09618759).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SYT15NM_031912.5 linkc.169C>T p.Arg57Trp missense_variant Exon 2 of 8 ENST00000374321.9 NP_114118.2 Q9BQS2-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SYT15ENST00000374321.9 linkc.169C>T p.Arg57Trp missense_variant Exon 2 of 8 2 NM_031912.5 ENSP00000363441.4 Q9BQS2-1
SYT15ENST00000503753.5 linkc.169C>T p.Arg57Trp missense_variant Exon 2 of 9 1 ENSP00000427607.1 Q9BQS2-2
SYT15ENST00000374323.8 linkc.372-569C>T intron_variant Intron 1 of 6 2 ENSP00000363443.3
SYT15ENST00000512997.5 linkc.7+1150C>T intron_variant Intron 1 of 2 2 ENSP00000424803.1 D6RF99

Frequencies

GnomAD3 genomes
AF:
0.00000981
AC:
1
AN:
101934
Hom.:
0
Cov.:
13
show subpopulations
Gnomad AFR
AF:
0.0000475
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:
0.0000805
AC:
20
AN:
248584
Hom.:
0
AF XY:
0.0000667
AC XY:
9
AN XY:
135030
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000557
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.0000931
Gnomad NFE exome
AF:
0.000133
Gnomad OTH exome
AF:
0.000165
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.00000910
AC:
5
AN:
549184
Hom.:
0
Cov.:
7
AF XY:
0.00000358
AC XY:
1
AN XY:
279482
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000526
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000255
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000790
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000981
AC:
1
AN:
101934
Hom.:
0
Cov.:
13
AF XY:
0.0000207
AC XY:
1
AN XY:
48376
show subpopulations
Gnomad4 AFR
AF:
0.0000475
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

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Dec 01, 2022
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.169C>T (p.R57W) alteration is located in exon 2 (coding exon 2) of the SYT15 gene. This alteration results from a C to T substitution at nucleotide position 169, causing the arginine (R) at amino acid position 57 to be replaced by a tryptophan (W). 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
0.088
BayesDel_noAF
Benign
-0.80
CADD
Benign
15
DANN
Uncertain
0.99
DEOGEN2
Benign
0.044
T;.
LIST_S2
Benign
0.42
T;.
MetaRNN
Benign
0.096
T;T
PROVEAN
Benign
-0.16
N;N
Sift
Uncertain
0.016
D;D
Sift4G
Uncertain
0.015
D;D
Vest4
0.14
gMVP
0.30

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.040
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: rs782702981; hg19: chr10-46969292; API