Variant X-38054386-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_138780.3(SYTL5):c.293A>G(p.Asn98Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000823 in 1,209,625 control chromosomes in the GnomAD database, including 2 homozygotes. There are 284 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0031 ( 1 hom., 97 hem., cov: 22)

Exomes 𝑓: 0.00059 ( 1 hom. 187 hem. )

Consequence

SYTL5
NM_138780.3 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 4.29

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 -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009031773).

BP6

Variant X-38054386-A-G is Benign according to our data. Variant chrX-38054386-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 3049119.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Hemizygotes in GnomAd4 at 97 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SYTL5	NM_138780.3 linkuse as main transcript	c.293A>G	p.Asn98Ser	missense_variant	3/17	ENST00000297875.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SYTL5	ENST00000297875.7 linkuse as main transcript	c.293A>G	p.Asn98Ser	missense_variant	3/17	5	NM_138780.3	P4	Q8TDW5-1
SYTL5	ENST00000456733.2 linkuse as main transcript	c.293A>G	p.Asn98Ser	missense_variant	2/17	1		A1	Q8TDW5-2

Frequencies

GnomAD3 genomes

AF:

0.00312

AC:

348

AN:

111535

Hom.:

Cov.:

AF XY:

0.00288

AC XY:

AN XY:

33693

show subpopulations

Gnomad AFR

AF:

0.00966

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000668

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000280

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00447

Gnomad MID

AF:

0.00840

Gnomad NFE

AF:

0.000207

Gnomad OTH

AF:

0.00268

GnomAD3 exomes

AF:

0.00131

AC:

240

AN:

182741

Hom.:

AF XY:

0.000949

AC XY:

AN XY:

67409

show subpopulations

Gnomad AFR exome

AF:

0.00958

Gnomad AMR exome

AF:

0.000730

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000578

Gnomad SAS exome

AF:

0.000157

Gnomad FIN exome

AF:

0.00431

Gnomad NFE exome

AF:

0.000135

Gnomad OTH exome

AF:

0.000664

GnomAD4 exome

AF:

0.000589

AC:

647

AN:

1098038

Hom.:

Cov.:

AF XY:

0.000515

AC XY:

187

AN XY:

363416

show subpopulations

Gnomad4 AFR exome

AF:

0.0111

Gnomad4 AMR exome

AF:

0.000625

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000397

Gnomad4 SAS exome

AF:

0.0000739

Gnomad4 FIN exome

AF:

0.00489

Gnomad4 NFE exome

AF:

0.0000819

Gnomad4 OTH exome

AF:

0.000998

GnomAD4 genome

AF:

0.00313

AC:

349

AN:

111587

Hom.:

Cov.:

AF XY:

0.00287

AC XY:

AN XY:

33755

show subpopulations

Gnomad4 AFR

AF:

0.00967

Gnomad4 AMR

AF:

0.000667

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000281

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00447

Gnomad4 NFE

AF:

0.000207

Gnomad4 OTH

AF:

0.00265

Alfa

AF:

0.000425

Hom.:

Bravo

AF:

0.00363

ESP6500AA

AF:

0.00939

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00128

AC:

155

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

SYTL5-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Dec 03, 2019

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

0.060

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.68

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.11

T;.

FATHMM_MKL

Uncertain

0.86

LIST_S2

Benign

0.33

T;T

MetaRNN

Benign

0.0090

T;T

MetaSVM

Benign

-0.83

MutationAssessor

Benign

0.83

L;L

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.39

PROVEAN

Benign

-1.1

N;N

REVEL

Benign

0.26

Sift

Benign

0.11

T;T

Sift4G

Benign

0.096

T;T

Polyphen

0.0010

B;.

Vest4

0.14

MVP

0.35

MPC

0.034

ClinPred

0.012

GERP RS

5.5

Varity_R

0.097

gMVP

0.14

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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