Variant 10-46583861-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_031912.5(SYT15):c.781C>G(p.Arg261Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000523 in 1,553,828 control chromosomes in the GnomAD database, including 96 homozygotes. In-silico tool predicts a benign outcome for this variant. 8/11 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00054 ( 9 hom., cov: 22)

Exomes 𝑓: 0.00052 ( 87 hom. )

Consequence

SYT15
NM_031912.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.50

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]

SYT15 links:

SYT15-AS1 (HGNC:56167): (SYT15 antisense RNA 1)

SYT15-AS1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.013980776).

BS2

High Homozygotes in GnomAd4 at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SYT15	NM_031912.5 link	c.781C>G	p.Arg261Gly	missense_variant	5/8	ENST00000374321.9	NP_114118.2	Q9BQS2-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SYT15	ENST00000374321.9 link	c.781C>G	p.Arg261Gly	missense_variant	5/8	2	NM_031912.5	ENSP00000363441.4		Q9BQS2-1

Frequencies

GnomAD3 genomes

AF:

0.000543

AC:

AN:

141896

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000167

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000278

Gnomad ASJ

AF:

0.0113

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000442

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000466

AC:

116

AN:

249124

Hom.:

AF XY:

0.000481

AC XY:

AN XY:

135142

show subpopulations

Gnomad AFR exome

AF:

0.0000646

Gnomad AMR exome

AF:

0.0000869

Gnomad ASJ exome

AF:

0.00761

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000359

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000142

Gnomad OTH exome

AF:

0.00149

GnomAD4 exome

AF:

0.000521

AC:

736

AN:

1411932

Hom.:

Cov.:

AF XY:

0.000548

AC XY:

384

AN XY:

701234

show subpopulations

Gnomad4 AFR exome

AF:

0.000234

Gnomad4 AMR exome

AF:

0.000266

Gnomad4 ASJ exome

AF:

0.0120

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000531

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000242

Gnomad4 OTH exome

AF:

0.00131

GnomAD4 genome

AF:

0.000543

AC:

AN:

141896

Hom.:

Cov.:

AF XY:

0.000535

AC XY:

AN XY:

69154

show subpopulations

Gnomad4 AFR

AF:

0.000167

Gnomad4 AMR

AF:

0.000278

Gnomad4 ASJ

AF:

0.0113

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000442

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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 19, 2022

The c.781C>G (p.R261G) alteration is located in exon 5 (coding exon 5) of the SYT15 gene. This alteration results from a C to G substitution at nucleotide position 781, causing the arginine (R) at amino acid position 261 to be replaced by a glycine (G). 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

0.089

BayesDel_noAF

Benign

-0.54

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.0072

T;T;.;.

LIST_S2

Benign

0.62

.;T;.;T

MetaRNN

Benign

0.014

T;T;T;T

PROVEAN

Benign

-1.5

N;N;N;N

Sift

Benign

0.33

T;T;T;T

Sift4G

Benign

0.23

T;T;T;T

Vest4

0.32

gMVP

0.89

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over