11-45252661-C-A

Position:

chr11-45252661-C-A

Variant summary

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

The NM_020826.3(SYT13):c.606G>T(p.Arg202Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000484 in 1,611,202 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00018 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00052 ( 1 hom. )

Consequence

SYT13
NM_020826.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.507

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:

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=0.028119206).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SYT13	NM_020826.3 linkuse as main transcript	c.606G>T	p.Arg202Ser	missense_variant	4/6	ENST00000020926.8	NP_065877.1	Q7L8C5
SYT13	NM_001247987.2 linkuse as main transcript	c.174G>T	p.Arg58Ser	missense_variant	6/8		NP_001234916.1
SYT13	XM_047427338.1 linkuse as main transcript	c.174G>T	p.Arg58Ser	missense_variant	4/6		XP_047283294.1
SYT13	XM_047427339.1 linkuse as main transcript	c.174G>T	p.Arg58Ser	missense_variant	4/6		XP_047283295.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SYT13	ENST00000020926.8 linkuse as main transcript	c.606G>T	p.Arg202Ser	missense_variant	4/6	1	NM_020826.3	ENSP00000020926.3	Q7L8C5
SYT13	ENST00000533332.1 linkuse as main transcript	n.*623G>T		non_coding_transcript_exon_variant	6/8	1		ENSP00000434967.1	H0YE47
SYT13	ENST00000533332.1 linkuse as main transcript	n.*623G>T		3_prime_UTR_variant	6/8	1		ENSP00000434967.1	H0YE47
SYT13	ENST00000528101.1 linkuse as main transcript	c.483G>T	p.Arg161Ser	missense_variant	4/4	4		ENSP00000432975.1	H0YD47

Frequencies

GnomAD3 genomes

AF:

0.000184

AC:

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

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:

0.0000942

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000368

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000229

AC:

AN:

248590

Hom.:

AF XY:

0.000208

AC XY:

AN XY:

134436

show subpopulations

Gnomad AFR exome

AF:

0.000246

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000463

Gnomad NFE exome

AF:

0.000467

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000515

AC:

752

AN:

1459006

Hom.:

Cov.:

AF XY:

0.000481

AC XY:

349

AN XY:

725196

show subpopulations

Gnomad4 AFR exome

AF:

0.000120

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000375

Gnomad4 NFE exome

AF:

0.000660

Gnomad4 OTH exome

AF:

0.000216

GnomAD4 genome

AF:

0.000184

AC:

AN:

152196

Hom.:

Cov.:

AF XY:

0.000188

AC XY:

AN XY:

74346

show subpopulations

Gnomad4 AFR

AF:

0.0000482

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.000368

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000384

Hom.:

Bravo

AF:

0.000212

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000239

AC:

EpiCase

AF:

0.000273

EpiControl

AF:

0.000237

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

Apr 01, 2024

The c.606G>T (p.R202S) alteration is located in exon 4 (coding exon 4) of the SYT13 gene. This alteration results from a G to T substitution at nucleotide position 606, causing the arginine (R) at amino acid position 202 to be replaced by a serine (S). 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

0.13

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.57

CADD

Benign

DANN

Benign

0.81

DEOGEN2

Benign

0.040

Eigen

Benign

-0.72

Eigen_PC

Benign

-0.64

FATHMM_MKL

Benign

0.086

LIST_S2

Benign

0.62

M_CAP

Benign

0.0051

MetaRNN

Benign

0.028

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.0

PrimateAI

Benign

0.31

PROVEAN

Benign

0.46

REVEL

Benign

0.046

Sift

Benign

0.21

Sift4G

Benign

0.34

Polyphen

0.0

Vest4

0.20

MutPred

0.40

Gain of disorder (P = 0.0515);

MVP

0.30

MPC

0.25

ClinPred

0.026

GERP RS

2.8

Varity_R

0.14

gMVP

0.30

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