X-100678480-T-C

Variant names:

• chrX-100678480-T-C
• NM_001370165.1:c.1778A>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.11

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]

ACMG classification

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
SYTL4	NM_001370165.1	c.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
SYTL4	ENST00000372989.6	c.1778A>G	p.Gln593Arg	missense_variant	Exon 19 of 20	1	NM_001370165.1	ENSP00000362080.1

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

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;