Variant X-38094302-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.839G>A(p.Gly280Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000501 in 1,197,554 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 20 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00030 ( 0 hom., 7 hem., cov: 22)

Exomes 𝑓: 0.000025 ( 0 hom. 13 hem. )

Consequence

SYTL5
NM_138780.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.520

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.06781542).

BS2

High Hemizygotes in GnomAd4 at 7 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SYTL5	NM_138780.3 linkuse as main transcript	c.839G>A	p.Gly280Asp	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.839G>A	p.Gly280Asp	missense_variant	8/17	5	NM_138780.3	P4	Q8TDW5-1
SYTL5	ENST00000456733.2 linkuse as main transcript	c.839G>A	p.Gly280Asp	missense_variant	7/17	1		A1	Q8TDW5-2

Frequencies

GnomAD3 genomes

AF:

0.000297

AC:

AN:

111133

Hom.:

Cov.:

AF XY:

0.000210

AC XY:

AN XY:

33391

show subpopulations

Gnomad AFR

AF:

0.000984

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000287

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000493

AC:

AN:

182426

Hom.:

AF XY:

0.0000596

AC XY:

AN XY:

67058

show subpopulations

Gnomad AFR exome

AF:

0.000532

Gnomad AMR exome

AF:

0.0000734

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000249

AC:

AN:

1086373

Hom.:

Cov.:

AF XY:

0.0000367

AC XY:

AN XY:

353955

show subpopulations

Gnomad4 AFR exome

AF:

0.000838

Gnomad4 AMR exome

AF:

0.0000570

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000660

GnomAD4 genome

AF:

0.000297

AC:

AN:

111181

Hom.:

Cov.:

AF XY:

0.000209

AC XY:

AN XY:

33449

show subpopulations

Gnomad4 AFR

AF:

0.000981

Gnomad4 AMR

AF:

0.000287

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000283

Hom.:

Bravo

AF:

0.000363

ESP6500AA

AF:

0.000261

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000412

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

Feb 21, 2024

The c.839G>A (p.G280D) alteration is located in exon 8 (coding exon 7) of the SYTL5 gene. This alteration results from a G to A substitution at nucleotide position 839, causing the glycine (G) at amino acid position 280 to be replaced by an aspartic acid (D). 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

0.090

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.54

CADD

Benign

DANN

Benign

0.90

DEOGEN2

Benign

0.019

T;.

FATHMM_MKL

Benign

0.75

LIST_S2

Benign

0.62

T;T

M_CAP

Benign

0.011

MetaRNN

Benign

0.068

T;T

MetaSVM

Benign

-0.74

MutationAssessor

Uncertain

2.5

M;M

MutationTaster

Benign

0.94

D;D;D

PrimateAI

Benign

0.41

PROVEAN

Benign

-2.3

N;N

REVEL

Benign

0.15

Sift

Benign

0.30

T;T

Sift4G

Uncertain

0.016

D;D

Polyphen

0.89

P;.

Vest4

0.16

MVP

0.23

MPC

0.045

ClinPred

0.12

GERP RS

3.1

Varity_R

0.13

gMVP

0.48

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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