Variant X-38054388-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4BP6BS2

The NM_138780.3(SYTL5):c.295G>C(p.Gly99Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000967 in 1,209,416 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 34 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.000099 ( 0 hom., 2 hem., cov: 22)

Exomes 𝑓: 0.000097 ( 0 hom. 32 hem. )

Consequence

SYTL5
NM_138780.3 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: 3.64

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 Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.29250368).

BP6

Variant X-38054388-G-C is Benign according to our data. Variant chrX-38054388-G-C is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 2378747.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}. Variant chrX-38054388-G-C is described in Lovd as [Likely_benign].

BS2

High Hemizygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SYTL5	NM_138780.3 linkuse as main transcript	c.295G>C	p.Gly99Arg	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.295G>C	p.Gly99Arg	missense_variant	3/17	5	NM_138780.3	P4	Q8TDW5-1
SYTL5	ENST00000456733.2 linkuse as main transcript	c.295G>C	p.Gly99Arg	missense_variant	2/17	1		A1	Q8TDW5-2

Frequencies

GnomAD3 genomes

AF:

0.0000987

AC:

AN:

111395

Hom.:

Cov.:

AF XY:

0.0000595

AC XY:

AN XY:

33593

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000573

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:

0.0000942

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000104

AC:

AN:

182653

Hom.:

AF XY:

0.0000742

AC XY:

AN XY:

67355

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000402

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:

0.0000985

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000965

AC:

106

AN:

1098021

Hom.:

Cov.:

AF XY:

0.0000881

AC XY:

AN XY:

363401

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000369

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:

0.0000926

Gnomad4 OTH exome

AF:

0.000304

GnomAD4 genome

AF:

0.0000987

AC:

AN:

111395

Hom.:

Cov.:

AF XY:

0.0000595

AC XY:

AN XY:

33593

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000573

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000942

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000907

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000149

AC:

ExAC

AF:

0.0000247

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.00

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 10, 2022

The c.295G>C (p.G99R) alteration is located in exon 3 (coding exon 2) of the SYTL5 gene. This alteration results from a G to C substitution at nucleotide position 295, causing the glycine (G) at amino acid position 99 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Mar 01, 2023

SYTL5: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.13

CADD

Benign

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.37

T;.

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.79

T;T

M_CAP

Uncertain

0.11

MetaRNN

Benign

0.29

T;T

MetaSVM

Uncertain

0.064

MutationAssessor

Uncertain

2.2

M;M

MutationTaster

Benign

0.67

N;N;N

PrimateAI

Uncertain

0.61

PROVEAN

Pathogenic

-4.7

D;D

REVEL

Uncertain

0.42

Sift

Uncertain

0.0010

D;D

Sift4G

Benign

0.099

T;T

Polyphen

0.92

P;.

Vest4

0.41

MVP

0.58

MPC

0.15

ClinPred

0.28

GERP RS

5.5

Varity_R

0.78

gMVP

0.52

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