X-100678480-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001370165.1(SYTL4):​c.1778A>G​(p.Gln593Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 22)

Consequence

SYTL4
NM_001370165.1 missense

Scores

3
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.11
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.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.25530532).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SYTL4NM_001370165.1 linkc.1778A>G p.Gln593Arg missense_variant Exon 19 of 20 ENST00000372989.6 NP_001357094.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SYTL4ENST00000372989.6 linkc.1778A>G p.Gln593Arg missense_variant Exon 19 of 20 1 NM_001370165.1 ENSP00000362080.1 Q96C24-1

Frequencies

GnomAD3 genomes
Cov.:
22
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
22

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Sep 10, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1778A>G (p.Q593R) alteration is located in exon 18 (coding exon 15) of the SYTL4 gene. This alteration results from a A to G substitution at nucleotide position 1778, causing the glutamine (Q) at amino acid position 593 to be replaced by an arginine (R). 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
0.097
BayesDel_addAF
Benign
-0.11
T
BayesDel_noAF
Benign
-0.39
CADD
Benign
21
DANN
Uncertain
1.0
DEOGEN2
Benign
0.098
T;T;T
FATHMM_MKL
Uncertain
0.90
D
LIST_S2
Benign
0.77
.;T;.
M_CAP
Benign
0.063
D
MetaRNN
Benign
0.26
T;T;T
MetaSVM
Benign
-0.83
T
MutationAssessor
Benign
0.58
N;N;N
PrimateAI
Uncertain
0.50
T
PROVEAN
Benign
-0.56
N;N;N
REVEL
Benign
0.084
Sift
Benign
0.32
T;T;T
Sift4G
Benign
0.26
T;T;T
Polyphen
0.54
P;P;P
Vest4
0.17
MutPred
0.39
Gain of sheet (P = 0.0827);Gain of sheet (P = 0.0827);Gain of sheet (P = 0.0827);
MVP
0.41
ClinPred
0.74
D
GERP RS
4.9
Varity_R
0.25
gMVP
0.20

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

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-99933477; API