chrX-100679401-C-T

Variant names:

• chrX-100679401-C-T
• rs140740598
• NM_001370165.1:c.1570G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001370165.1(SYTL4):​c.1570G>A​(p.Glu524Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000261 in 1,205,157 control chromosomes in the GnomAD database, including 1 homozygotes. There are 107 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00020 (0 hom., 4 hem., cov: 22)
  • Exomes 𝑓: 0.00027 (1 hom. 103 hem.)
• Consequence: SYTL4 NM_001370165.1 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.34
• Publications: 2 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: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.03453383).
• BP6: Variant X-100679401-C-T is Benign according to our data. Variant chrX-100679401-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2661038.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Hemizygotes in GnomAd4 at 4 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYTL4	NM_001370165.1	MANE Select	c.1570G>A	p.Glu524Lys	missense	Exon 18 of 20	NP_001357094.1	Q96C24-1
	SYTL4	NM_001370162.1		c.1570G>A	p.Glu524Lys	missense	Exon 16 of 19	NP_001357091.1
	SYTL4	NM_001129896.3		c.1570G>A	p.Glu524Lys	missense	Exon 16 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.1570G>A	p.Glu524Lys	missense	Exon 18 of 20	ENSP00000362080.1	Q96C24-1
	SYTL4	ENST00000276141.10	TSL:1	c.1570G>A	p.Glu524Lys	missense	Exon 15 of 17	ENSP00000276141.6	Q96C24-1
	SYTL4	ENST00000263033.9	TSL:2	c.1570G>A	p.Glu524Lys	missense	Exon 15 of 17	ENSP00000263033.5	Q96C24-1

Frequencies

GnomAD3 genomes AF: 0.000197 AC: 22 AN: 111631 Hom.: 0 Cov.: 22

Gnomad AFR AF: 0.0000652

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000953

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000328

Gnomad MID AF: 0.00417

Gnomad NFE AF: 0.000226

Gnomad OTH AF: 0.00266

GnomAD2 exomes AF: 0.000312 AC: 57 AN: 182767 AF XY: 0.000312

Gnomad AFR exome AF: 0.0000761

Gnomad AMR exome AF: 0.000147

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000250

Gnomad NFE exome AF: 0.000502

Gnomad OTH exome AF: 0.000222

GnomAD4 exome AF: 0.000267 AC: 292 AN: 1093471 Hom.: 1 Cov.: 29 AF XY: 0.000287 AC XY: 103 AN XY: 358957

African (AFR) AF: 0.0000380 AC: 1 AN: 26319

American (AMR) AF: 0.000227 AC: 8 AN: 35191

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19351

East Asian (EAS) AF: 0.00 AC: 0 AN: 30186

South Asian (SAS) AF: 0.000296 AC: 16 AN: 53971

European-Finnish (FIN) AF: 0.000346 AC: 14 AN: 40508

Middle Eastern (MID) AF: 0.00268 AC: 11 AN: 4099

European-Non Finnish (NFE) AF: 0.000260 AC: 218 AN: 837919

Other (OTH) AF: 0.000523 AC: 24 AN: 45927

GnomAD4 genome AF: 0.000197 AC: 22 AN: 111686 Hom.: 0 Cov.: 22 AF XY: 0.000118 AC XY: 4 AN XY: 33862

African (AFR) AF: 0.0000651 AC: 2 AN: 30744

American (AMR) AF: 0.0000951 AC: 1 AN: 10510

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2648

East Asian (EAS) AF: 0.00 AC: 0 AN: 3553

South Asian (SAS) AF: 0.00 AC: 0 AN: 2603

European-Finnish (FIN) AF: 0.000328 AC: 2 AN: 6089

Middle Eastern (MID) AF: 0.00457 AC: 1 AN: 219

European-Non Finnish (NFE) AF: 0.000226 AC: 12 AN: 53116

Other (OTH) AF: 0.00263 AC: 4 AN: 1523

Alfa AF: 0.000443 Hom.: 18

Bravo AF: 0.000170

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000346 AC: 1

ESP6500AA AF: 0.000261 AC: 1

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000461 AC: 56

EpiCase AF: 0.000818

EpiControl AF: 0.000832

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.55	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.043	T
FATHMM_MKL	Benign	0.69	D
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.035	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.25	N
PhyloP100		3.3
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	0.36	N
REVEL	Benign	0.050
Sift	Benign	0.20	T
Sift4G	Benign	0.94	T
Polyphen		0.049	B
Vest4		0.14
MVP		0.20
ClinPred		0.014	T
GERP RS		4.0
Varity_R		0.21
gMVP		0.33
Mutation Taster		=100/0	polymorphism

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: rs140740598; hg19: chrX-99934398;