chrX-100686110-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.

The NM_001370165.1(SYTL4):​c.1329G>T​(p.Gln443His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000414 in 1,208,725 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000089 ( 0 hom., 1 hem., cov: 23)
Exomes 𝑓: 0.0000036 ( 0 hom. 1 hem. )

Consequence

SYTL4
NM_001370165.1 missense

Scores

1
10
6

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.840
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SYTL4NM_001370165.1 linkc.1329G>T p.Gln443His missense_variant Exon 16 of 20 ENST00000372989.6 NP_001357094.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SYTL4ENST00000372989.6 linkc.1329G>T p.Gln443His missense_variant Exon 16 of 20 1 NM_001370165.1 ENSP00000362080.1 Q96C24-1

Frequencies

GnomAD3 genomes
AF:
0.00000892
AC:
1
AN:
112075
Hom.:
0
Cov.:
23
AF XY:
0.0000292
AC XY:
1
AN XY:
34231
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:
0.0000188
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.00000365
AC:
4
AN:
1096650
Hom.:
0
Cov.:
29
AF XY:
0.00000276
AC XY:
1
AN XY:
362062
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
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:
0.00000475
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000892
AC:
1
AN:
112075
Hom.:
0
Cov.:
23
AF XY:
0.0000292
AC XY:
1
AN XY:
34231
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000188
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000151

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Feb 25, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1329G>T (p.Q443H) alteration is located in exon 15 (coding exon 12) of the SYTL4 gene. This alteration results from a G to T substitution at nucleotide position 1329, causing the glutamine (Q) at amino acid position 443 to be replaced by a histidine (H). 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
Uncertain
0.35
BayesDel_addAF
Uncertain
0.13
D
BayesDel_noAF
Uncertain
-0.050
CADD
Benign
19
DANN
Uncertain
1.0
DEOGEN2
Benign
0.36
T;T;T
FATHMM_MKL
Uncertain
0.79
D
LIST_S2
Benign
0.80
.;T;.
M_CAP
Pathogenic
0.61
D
MetaRNN
Uncertain
0.71
D;D;D
MetaSVM
Benign
-0.80
T
MutationAssessor
Benign
1.7
L;L;L
PrimateAI
Uncertain
0.56
T
PROVEAN
Uncertain
-3.6
D;D;D
REVEL
Uncertain
0.35
Sift
Uncertain
0.0020
D;D;D
Sift4G
Benign
0.15
T;T;T
Polyphen
0.37
B;B;B
Vest4
0.46
MutPred
0.55
Loss of MoRF binding (P = 0.115);Loss of MoRF binding (P = 0.115);Loss of MoRF binding (P = 0.115);
MVP
0.62
ClinPred
0.97
D
GERP RS
2.1
Varity_R
0.89
gMVP
0.62

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
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.

Other links and lift over

dbSNP: rs1227033878; hg19: chrX-99941107; API