Variant 11-45254315-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_020826.3(SYT13):c.499G>A(p.Asp167Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000154 in 1,613,456 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00024 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00015 ( 0 hom. )

Consequence

SYT13
NM_020826.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.481

Variant links:

Genes affected

SYT13 (HGNC:14962): (synaptotagmin 13) This gene encodes a member of the large synaptotagmin protein family. Family members have an extracellular N-terminal transmembrane domain and a cytoplasmic C terminus with two tandem C2 domains (C2A and C2B). Synaptotogmin family members can form homo- and heteromeric complexes with each other. They also have different biochemical properties and developmental profiles, and patterns of tissue distribution. Synaptotagmins function as membrane traffickers in multicellular organisms. Two alternatively spliced transcript variants that encode different protein isoforms have been described for this gene. [provided by RefSeq, Oct 2011]

SYT13 links:

ENSG00000254497 (HGNC:):

ENSG00000254497 links:

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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=0.011742443).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SYT13	NM_020826.3 linkuse as main transcript	c.499G>A	p.Asp167Asn	missense_variant	3/6	ENST00000020926.8	NP_065877.1	Q7L8C5
SYT13	NM_001247987.2 linkuse as main transcript	c.67G>A	p.Asp23Asn	missense_variant	5/8		NP_001234916.1
SYT13	XM_047427338.1 linkuse as main transcript	c.67G>A	p.Asp23Asn	missense_variant	3/6		XP_047283294.1
SYT13	XM_047427339.1 linkuse as main transcript	c.67G>A	p.Asp23Asn	missense_variant	3/6		XP_047283295.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SYT13	ENST00000020926.8 linkuse as main transcript	c.499G>A	p.Asp167Asn	missense_variant	3/6	1	NM_020826.3	ENSP00000020926.3		Q7L8C5

Frequencies

GnomAD3 genomes

AF:

0.000243

AC:

AN:

152180

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00105

Gnomad ASJ

AF:

0.00548

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000359

AC:

AN:

250474

Hom.:

AF XY:

0.000362

AC XY:

AN XY:

135382

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000410

Gnomad ASJ exome

AF:

0.00646

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000793

Gnomad OTH exome

AF:

0.000329

GnomAD4 exome

AF:

0.000145

AC:

212

AN:

1461276

Hom.:

Cov.:

AF XY:

0.000150

AC XY:

109

AN XY:

726898

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000291

Gnomad4 ASJ exome

AF:

0.00609

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000207

Gnomad4 OTH exome

AF:

0.000265

GnomAD4 genome

AF:

0.000243

AC:

AN:

152180

Hom.:

Cov.:

AF XY:

0.000215

AC XY:

AN XY:

74344

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00105

Gnomad4 ASJ

AF:

0.00548

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000707

Hom.:

Bravo

AF:

0.000185

ExAC

AF:

0.000214

AC:

EpiCase

AF:

0.0000546

EpiControl

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

May 25, 2022

The c.499G>A (p.D167N) alteration is located in exon 3 (coding exon 3) of the SYT13 gene. This alteration results from a G to A substitution at nucleotide position 499, causing the aspartic acid (D) at amino acid position 167 to be replaced by an asparagine (N). 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

0.084

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.70

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.046

Eigen

Benign

-0.17

Eigen_PC

Benign

-0.070

FATHMM_MKL

Benign

0.48

LIST_S2

Benign

0.60

M_CAP

Benign

0.0078

MetaRNN

Benign

0.012

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

PrimateAI

Benign

0.38

PROVEAN

Benign

-1.1

REVEL

Benign

0.049

Sift

Benign

0.076

Sift4G

Benign

0.70

Polyphen

0.0

Vest4

0.22

MVP

0.51

MPC

0.22

ClinPred

0.018

GERP RS

2.6

Varity_R

0.056

gMVP

0.39

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