Variant chrX-38094410-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_138780.3(SYTL5):c.947C>T(p.Thr316Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000482 in 1,195,776 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 178 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0015 ( 0 hom., 41 hem., cov: 23)

Exomes 𝑓: 0.00038 ( 0 hom. 137 hem. )

Consequence

SYTL5
NM_138780.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.637

Variant links:

Genes affected

SYTL5 (HGNC:15589): (synaptotagmin like 5) The protein encoded by this gene belongs to the synaptotagmin-like (Slp) protein family, which contains a unique homology domain at the N-terminus, referred to as the Slp homology domain (SHD). The SHD functions as a binding site for Rab27A, which plays a role in protein transport. Expression of this gene is restricted to placenta and liver, suggesting that it might be involved in Rab27A-dependent membrane trafficking in specific tissues. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2009]

SYTL5 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0059408545).

BP6

Variant X-38094410-C-T is Benign according to our data. Variant chrX-38094410-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3046489.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAd4 at 41 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SYTL5	NM_138780.3 linkuse as main transcript	c.947C>T	p.Thr316Ile	missense_variant	8/17	ENST00000297875.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SYTL5	ENST00000297875.7 linkuse as main transcript	c.947C>T	p.Thr316Ile	missense_variant	8/17	5	NM_138780.3	P4	Q8TDW5-1
SYTL5	ENST00000456733.2 linkuse as main transcript	c.947C>T	p.Thr316Ile	missense_variant	7/17	1		A1	Q8TDW5-2

Frequencies

GnomAD3 genomes

AF:

0.00151

AC:

168

AN:

111234

Hom.:

Cov.:

AF XY:

0.00123

AC XY:

AN XY:

33436

show subpopulations

Gnomad AFR

AF:

0.00389

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00201

Gnomad ASJ

AF:

0.000378

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0170

Gnomad NFE

AF:

0.000359

Gnomad OTH

AF:

0.00266

GnomAD3 exomes

AF:

0.000772

AC:

141

AN:

182618

Hom.:

AF XY:

0.000580

AC XY:

AN XY:

67226

show subpopulations

Gnomad AFR exome

AF:

0.00433

Gnomad AMR exome

AF:

0.00191

Gnomad ASJ exome

AF:

0.000268

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000307

Gnomad OTH exome

AF:

0.00111

GnomAD4 exome

AF:

0.000376

AC:

408

AN:

1084486

Hom.:

Cov.:

AF XY:

0.000389

AC XY:

137

AN XY:

352018

show subpopulations

Gnomad4 AFR exome

AF:

0.00465

Gnomad4 AMR exome

AF:

0.00163

Gnomad4 ASJ exome

AF:

0.000262

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000194

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000197

Gnomad4 OTH exome

AF:

0.000859

GnomAD4 genome

AF:

0.00151

AC:

168

AN:

111290

Hom.:

Cov.:

AF XY:

0.00122

AC XY:

AN XY:

33502

show subpopulations

Gnomad4 AFR

AF:

0.00388

Gnomad4 AMR

AF:

0.00200

Gnomad4 ASJ

AF:

0.000378

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000359

Gnomad4 OTH

AF:

0.00263

Alfa

AF:

0.000233

Hom.:

Bravo

AF:

0.00200

TwinsUK

AF:

0.00135

AC:

ALSPAC

AF:

0.000346

AC:

ESP6500AA

AF:

0.00287

AC:

ESP6500EA

AF:

0.000297

AC:

ExAC

AF:

0.000610

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

SYTL5-related disorder

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 14, 2023

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.086

BayesDel_addAF

Benign

-0.86

BayesDel_noAF

Benign

-1.0

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.0057

T;.

FATHMM_MKL

Benign

0.046

LIST_S2

Benign

0.71

T;T

M_CAP

Benign

0.0049

MetaRNN

Benign

0.0059

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

L;L

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.28

PROVEAN

Benign

-0.28

N;N

REVEL

Benign

0.017

Sift

Benign

0.51

T;T

Sift4G

Benign

0.23

T;T

Polyphen

0.0

B;.

Vest4

0.048

MVP

0.28

MPC

0.038

ClinPred

0.0059

GERP RS

2.5

Varity_R

0.038

gMVP

0.15

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