Genetic Variant SYTL4:p.Glu487Lys (chrX-100681326-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_001370165.1(SYTL4):c.1459G>A(p.Glu487Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000832 in 1,202,150 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 3 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000027 ( 0 hom., 1 hem., cov: 22)

Exomes 𝑓: 0.0000064 ( 0 hom. 2 hem. )

Consequence

SYTL4
NM_001370165.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.64

Publications

0 publications found

Variant links:

Genes affected

SYTL4 (HGNC:15588): (synaptotagmin like 4) This gene encodes a member of the synaptotagmin like protein family. Members of this family are characterized by an N-terminal Rab27 binding domain and C-terminal tandem C2 domains. The encoded protein binds specific small Rab GTPases and is involved in intracellular membrane trafficking. This protein binds Rab27 and may be involved in inhibiting dense core vesicle exocytosis. Alternate splicing results in multiple transcript variants that encode the same protein. [provided by RefSeq, Mar 2010]

SYTL4 Gene-Disease associations (from GenCC):

retinal disorder
Inheritance: XL Classification: LIMITED Submitted by: Ambry Genetics

SYTL4 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BS2

High Hemizygotes in GnomAdExome4 at 2 XL gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001370165.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SYTL4	NM_001370165.1	MANE Select	c.1459G>A	p.Glu487Lys	missense	Exon 17 of 20	NP_001357094.1	Q96C24-1
SYTL4	NM_001370162.1		c.1459G>A	p.Glu487Lys	missense	Exon 15 of 19	NP_001357091.1
SYTL4	NM_001129896.3		c.1459G>A	p.Glu487Lys	missense	Exon 15 of 18	NP_001123368.1	Q96C24-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SYTL4	ENST00000372989.6	TSL:1 MANE Select	c.1459G>A	p.Glu487Lys	missense	Exon 17 of 20	ENSP00000362080.1	Q96C24-1
SYTL4	ENST00000276141.10	TSL:1	c.1459G>A	p.Glu487Lys	missense	Exon 14 of 17	ENSP00000276141.6	Q96C24-1
SYTL4	ENST00000263033.9	TSL:2	c.1459G>A	p.Glu487Lys	missense	Exon 14 of 17	ENSP00000263033.5	Q96C24-1

Frequencies

GnomAD3 genomes

AF:

0.0000269

AC:

AN:

111568

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000564

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000553

AC:

AN:

180952

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000124

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000642

AC:

AN:

1090526

Hom.:

Cov.:

AF XY:

0.00000562

AC XY:

AN XY:

355998

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26248

American (AMR)

AF:

0.00

AC:

AN:

35073

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19257

East Asian (EAS)

AF:

0.00

AC:

AN:

30127

South Asian (SAS)

AF:

0.00

AC:

AN:

53609

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40498

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4076

European-Non Finnish (NFE)

AF:

0.00000718

AC:

AN:

835793

Other (OTH)

AF:

0.0000218

AC:

AN:

45845

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000269

AC:

AN:

111624

Hom.:

Cov.:

AF XY:

0.0000296

AC XY:

AN XY:

33796

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30712

American (AMR)

AF:

0.00

AC:

AN:

10503

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2646

East Asian (EAS)

AF:

0.00

AC:

AN:

3554

South Asian (SAS)

AF:

0.00

AC:

AN:

2603

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6043

Middle Eastern (MID)

AF:

0.00

AC:

AN:

217

European-Non Finnish (NFE)

AF:

0.0000564

AC:

AN:

53149

Other (OTH)

AF:

0.00

AC:

AN:

1510

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000142

Hom.:

Bravo

AF:

0.0000113

ExAC

AF:

0.00000824

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.52

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.14

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.83

M_CAP

Benign

0.0066

MetaRNN

Benign

0.092

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.2

PhyloP100

5.6

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-1.3

REVEL

Benign

0.046

Sift

Benign

0.18

Sift4G

Benign

0.66

Polyphen

0.14

Vest4

0.21

MVP

0.17

ClinPred

0.29

GERP RS

5.1

Varity_R

0.39

gMVP

0.22

Mutation Taster

=99/1

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.22

Details are displayed if max score is > 0.2

DS_AL_spliceai

0.22

Position offset: 9

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over