Variant X-38089456-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_138780.3(SYTL5):c.700G>A(p.Gly234Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000176 in 1,205,630 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 57 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00018 ( 0 hom., 3 hem., cov: 23)

Exomes 𝑓: 0.00018 ( 0 hom. 54 hem. )

Consequence

SYTL5
NM_138780.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.63

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 -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.05286953).

BS2

High Hemizygotes in GnomAd4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SYTL5	NM_138780.3 linkuse as main transcript	c.700G>A	p.Gly234Ser	missense_variant	7/17	ENST00000297875.7	NP_620135.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SYTL5	ENST00000297875.7 linkuse as main transcript	c.700G>A	p.Gly234Ser	missense_variant	7/17	5	NM_138780.3	ENSP00000297875	P4	Q8TDW5-1
SYTL5	ENST00000456733.2 linkuse as main transcript	c.700G>A	p.Gly234Ser	missense_variant	6/17	1		ENSP00000395220	A1	Q8TDW5-2

Frequencies

GnomAD3 genomes

AF:

0.000180

AC:

AN:

111216

Hom.:

Cov.:

AF XY:

0.0000898

AC XY:

AN XY:

33412

show subpopulations

Gnomad AFR

AF:

0.000131

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000191

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000245

Gnomad OTH

AF:

0.000665

GnomAD3 exomes

AF:

0.000145

AC:

AN:

172173

Hom.:

AF XY:

0.0000345

AC XY:

AN XY:

58047

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000305

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000183

Gnomad OTH exome

AF:

0.000703

GnomAD4 exome

AF:

0.000175

AC:

192

AN:

1094414

Hom.:

Cov.:

AF XY:

0.000150

AC XY:

AN XY:

360342

show subpopulations

Gnomad4 AFR exome

AF:

0.0000762

Gnomad4 AMR exome

AF:

0.000433

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000248

Gnomad4 NFE exome

AF:

0.000199

Gnomad4 OTH exome

AF:

0.000152

GnomAD4 genome

AF:

0.000180

AC:

AN:

111216

Hom.:

Cov.:

AF XY:

0.0000898

AC XY:

AN XY:

33412

show subpopulations

Gnomad4 AFR

AF:

0.000131

Gnomad4 AMR

AF:

0.000191

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000245

Gnomad4 OTH

AF:

0.000665

Alfa

AF:

0.000380

Hom.:

Bravo

AF:

0.000306

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000346

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000446

AC:

ExAC

AF:

0.0000989

AC:

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

Dec 03, 2021

The c.700G>A (p.G234S) alteration is located in exon 7 (coding exon 6) of the SYTL5 gene. This alteration results from a G to A substitution at nucleotide position 700, causing the glycine (G) at amino acid position 234 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

0.073

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.91

CADD

Benign

DANN

Benign

0.75

DEOGEN2

Benign

0.0042

T;.

FATHMM_MKL

Benign

0.25

LIST_S2

Benign

0.79

T;T

M_CAP

Benign

0.053

MetaRNN

Benign

0.053

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

N;N

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.30

PROVEAN

Benign

0.13

N;N

REVEL

Benign

0.064

Sift

Benign

0.73

T;T

Sift4G

Benign

0.70

T;T

Polyphen

0.0060

B;.

Vest4

0.20

MVP

0.21

MPC

0.037

ClinPred

0.011

GERP RS

0.91

Varity_R

0.040

gMVP

0.15

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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