chrX-100686110-C-A

Variant names:

• chrX-100686110-C-A
• rs1227033878
• NM_001370165.1:c.1329G>T

Variant summary

Our verdict is Uncertain significance. The variant received 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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.840
• Publications: 0 publications found

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYTL4	NM_001370165.1	MANE Select	c.1329G>T	p.Gln443His	missense	Exon 16 of 20	NP_001357094.1	Q96C24-1
	SYTL4	NM_001370162.1		c.1329G>T	p.Gln443His	missense	Exon 14 of 19	NP_001357091.1
	SYTL4	NM_001129896.3		c.1329G>T	p.Gln443His	missense	Exon 14 of 18	NP_001123368.1	Q96C24-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYTL4	ENST00000372989.6	TSL:1 MANE Select	c.1329G>T	p.Gln443His	missense	Exon 16 of 20	ENSP00000362080.1	Q96C24-1
	SYTL4	ENST00000276141.10	TSL:1	c.1329G>T	p.Gln443His	missense	Exon 13 of 17	ENSP00000276141.6	Q96C24-1
	SYTL4	ENST00000263033.9	TSL:2	c.1329G>T	p.Gln443His	missense	Exon 13 of 17	ENSP00000263033.5	Q96C24-1

Frequencies

GnomAD3 genomes AF: 0.00000892 AC: 1 AN: 112075 Hom.: 0 Cov.: 23

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

African (AFR) AF: 0.00 AC: 0 AN: 26374

American (AMR) AF: 0.00 AC: 0 AN: 35111

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19357

East Asian (EAS) AF: 0.00 AC: 0 AN: 30167

South Asian (SAS) AF: 0.00 AC: 0 AN: 53627

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40449

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4134

European-Non Finnish (NFE) AF: 0.00000475 AC: 4 AN: 841404

Other (OTH) AF: 0.00 AC: 0 AN: 46027

GnomAD4 genome AF: 0.00000892 AC: 1 AN: 112075 Hom.: 0 Cov.: 23 AF XY: 0.0000292 AC XY: 1 AN XY: 34231

African (AFR) AF: 0.00 AC: 0 AN: 30813

American (AMR) AF: 0.00 AC: 0 AN: 10632

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2645

East Asian (EAS) AF: 0.00 AC: 0 AN: 3572

South Asian (SAS) AF: 0.00 AC: 0 AN: 2653

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6102

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 239

European-Non Finnish (NFE) AF: 0.0000188 AC: 1 AN: 53215

Other (OTH) AF: 0.00 AC: 0 AN: 1515

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000151

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Benign	0.80	T
M_CAP	Pathogenic	0.61	D
MetaRNN	Uncertain	0.71	D
MetaSVM	Benign	-0.80	T
MutationAssessor	Benign	1.7	L
PhyloP100		0.84
PrimateAI	Uncertain	0.56	T
PROVEAN	Uncertain	-3.6	D
REVEL	Uncertain	0.35
Sift	Uncertain	0.0020	D
Sift4G	Benign	0.15	T
Polyphen		0.37	B
Vest4		0.46
MutPred		0.55		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
Mutation Taster		=44/56	disease causing

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

Other links and lift over

dbSNP: rs1227033878; hg19: chrX-99941107;