chr11-45252702-C-T

Variant names:

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_020826.3(SYT13):c.565G>A(p.Gly189Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000252 in 1,427,998 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: not found (cov: 33)

Exomes 𝑓: 0.000025 ( 0 hom. )

Consequence

SYT13
NM_020826.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.802

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.25612205).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYT13	NM_020826.3 link	c.565G>A	p.Gly189Arg	missense_variant	Exon 4 of 6	ENST00000020926.8	NP_065877.1	Q7L8C5
SYT13	NM_001247987.2 link	c.133G>A	p.Gly45Arg	missense_variant	Exon 6 of 8		NP_001234916.1
SYT13	XM_047427338.1 link	c.133G>A	p.Gly45Arg	missense_variant	Exon 4 of 6		XP_047283294.1
SYT13	XM_047427339.1 link	c.133G>A	p.Gly45Arg	missense_variant	Exon 4 of 6		XP_047283295.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SYT13	ENST00000020926.8 link	c.565G>A	p.Gly189Arg	missense_variant	Exon 4 of 6	1	NM_020826.3	ENSP00000020926.3	Q7L8C5
SYT13	ENST00000533332.1 link	n.*582G>A		non_coding_transcript_exon_variant	Exon 6 of 8	1		ENSP00000434967.1	H0YE47
SYT13	ENST00000533332.1 link	n.*582G>A		3_prime_UTR_variant	Exon 6 of 8	1		ENSP00000434967.1	H0YE47
SYT13	ENST00000528101.1 link	c.442G>A	p.Gly148Arg	missense_variant	Exon 4 of 4	4		ENSP00000432975.1	H0YD47

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000852

AC:

AN:

234702

Hom.:

AF XY:

0.00000789

AC XY:

AN XY:

126770

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000110

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000252

AC:

AN:

1427998

Hom.:

Cov.:

AF XY:

0.0000298

AC XY:

AN XY:

704522

show subpopulations

Gnomad4 AFR exome

AF:

0.0000305

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000257

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000312

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Mar 03, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.565G>A (p.G189R) alteration is located in exon 4 (coding exon 4) of the SYT13 gene. This alteration results from a G to A substitution at nucleotide position 565, causing the glycine (G) at amino acid position 189 to be replaced by an arginine (R). 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

0.12

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.43

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.35

Eigen

Benign

-0.16

Eigen_PC

Benign

-0.23

FATHMM_MKL

Benign

0.24

LIST_S2

Benign

0.82

M_CAP

Benign

0.012

MetaRNN

Benign

0.26

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.8

PrimateAI

Benign

0.41

PROVEAN

Pathogenic

-4.7

REVEL

Benign

0.082

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.055

Polyphen

0.97

Vest4

0.32

MutPred

0.38

Gain of solvent accessibility (P = 0.0674);

MVP

0.42

MPC

0.27

ClinPred

0.95

GERP RS

4.9

Varity_R

0.52

gMVP

0.60

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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