rs7877841

Positions:

• chrX-100683797-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001370165.1(SYTL4):​c.1449+2193A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.13 in 111,804 control chromosomes in the GnomAD database, including 2,235 homozygotes. There are 3,992 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.13 (2235 hom., 3992 hem., cov: 23)
• Consequence: SYTL4 NM_001370165.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.313

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.439 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SYTL4	NM_001370165.1	c.1449+2193A>G		intron_variant		ENST00000372989.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SYTL4	ENST00000372989.6	c.1449+2193A>G		intron_variant		1	NM_001370165.1	P1
SYTL4	ENST00000276141.10	c.1449+2193A>G		intron_variant		1		P1
SYTL4	ENST00000263033.9	c.1449+2193A>G		intron_variant		2		P1
SYTL4	ENST00000685623.1	c.1449+2193A>G		intron_variant				P1

Frequencies

GnomAD3 genomes AF: 0.130 AC: 14517 AN: 111751 Hom.: 2229 Cov.: 23 AF XY: 0.117 AC XY: 3973 AN XY: 33973

Gnomad AFR AF: 0.445

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0560

Gnomad ASJ AF: 0.000757

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00594

Gnomad FIN AF: 0.000165

Gnomad MID AF: 0.0254

Gnomad NFE AF: 0.00343

Gnomad OTH AF: 0.107

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.130 AC: 14546 AN: 111804 Hom.: 2235 Cov.: 23 AF XY: 0.117 AC XY: 3992 AN XY: 34036

Gnomad4 AFR AF: 0.445

Gnomad4 AMR AF: 0.0558

Gnomad4 ASJ AF: 0.000757

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00559

Gnomad4 FIN AF: 0.000165

Gnomad4 NFE AF: 0.00343

Gnomad4 OTH AF: 0.105

Alfa AF: 0.0783 Hom.: 472

Bravo AF: 0.151

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	3.9
DANN	Benign	0.89

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

Other links and lift over

dbSNP: rs7877841; hg19: chrX-99938794;