Variant X-38094368-G-A 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.905G>A(p.Arg302His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000338 in 1,203,724 control chromosomes in the GnomAD database, including 5 homozygotes. There are 191 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R302C) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.00040 ( 0 hom., 15 hem., cov: 22)

Exomes 𝑓: 0.00033 ( 5 hom. 176 hem. )

Consequence

SYTL5
NM_138780.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.17

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=0.004324436).

BP6

Variant X-38094368-G-A is Benign according to our data. Variant chrX-38094368-G-A is described in ClinVar as [Benign]. Clinvar id is 3046743.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAd4 at 15 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SYTL5	NM_138780.3 linkuse as main transcript	c.905G>A	p.Arg302His	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.905G>A	p.Arg302His	missense_variant	8/17	5	NM_138780.3	P4	Q8TDW5-1
SYTL5	ENST00000456733.2 linkuse as main transcript	c.905G>A	p.Arg302His	missense_variant	7/17	1		A1	Q8TDW5-2

Frequencies

GnomAD3 genomes

AF:

0.000405

AC:

AN:

111147

Hom.:

Cov.:

AF XY:

0.000449

AC XY:

AN XY:

33387

show subpopulations

Gnomad AFR

AF:

0.000949

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00575

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000189

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000841

AC:

154

AN:

183011

Hom.:

AF XY:

0.00104

AC XY:

AN XY:

67603

show subpopulations

Gnomad AFR exome

AF:

0.00106

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000217

Gnomad SAS exome

AF:

0.00714

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000123

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000331

AC:

362

AN:

1092523

Hom.:

Cov.:

AF XY:

0.000491

AC XY:

176

AN XY:

358589

show subpopulations

Gnomad4 AFR exome

AF:

0.000646

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.000104

Gnomad4 EAS exome

AF:

0.0000995

Gnomad4 SAS exome

AF:

0.00557

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000286

Gnomad4 OTH exome

AF:

0.000415

GnomAD4 genome

AF:

0.000405

AC:

AN:

111201

Hom.:

Cov.:

AF XY:

0.000448

AC XY:

AN XY:

33451

show subpopulations

Gnomad4 AFR

AF:

0.000947

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00576

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000189

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000169

Hom.:

Bravo

AF:

0.000261

ESP6500AA

AF:

0.00104

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00110

AC:

134

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

SYTL5-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 20, 2019

This variant is classified as 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

0.064

BayesDel_addAF

Benign

-0.91

BayesDel_noAF

Benign

-1.1

CADD

Benign

0.11

DANN

Benign

0.83

DEOGEN2

Benign

0.0058

T;.

FATHMM_MKL

Benign

0.018

LIST_S2

Benign

0.25

T;T

MetaRNN

Benign

0.0043

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.57

N;N

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.17

PROVEAN

Benign

-0.93

N;N

REVEL

Benign

0.020

Sift

Benign

0.17

T;T

Sift4G

Benign

0.30

T;T

Polyphen

0.0020

B;.

Vest4

0.034

MVP

0.061

MPC

0.041

ClinPred

0.0047

GERP RS

-2.3

Varity_R

0.038

gMVP

0.18

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