rs4827330

chrX-38073633-A-GchrX-38073633-A-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BA1

The NM_138780.3(SYTL5):c.489A>G(p.Ala163=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.252 in 1,195,168 control chromosomes in the GnomAD database, including 27,479 homozygotes. There are 97,531 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in Lovd as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.29 (3865 hom., 9223 hem., cov: 22)
  • Exomes 𝑓: 0.25 (23614 hom. 88308 hem.)
• Consequence: SYTL5 NM_138780.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.198

Genes affected

SYTL5 (HGNC:15589): (synaptotagmin like 5) The protein encoded by this gene belongs to the synaptotagmin-like (Slp) protein family, which contains a unique homology domain at the N-terminus, referred to as the Slp homology domain (SHD). The SHD functions as a binding site for Rab27A, which plays a role in protein transport. Expression of this gene is restricted to placenta and liver, suggesting that it might be involved in Rab27A-dependent membrane trafficking in specific tissues. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2009]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant X-38073633-A-G is Benign according to our data. Variant chrX-38073633-A-G is described in Lovd as [Likely_benign].
• BP7: Synonymous conserved (PhyloP=-0.198 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.41 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SYTL5	NM_138780.3	c.489A>G	p.Ala163=	synonymous_variant	5/17	ENST00000297875.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SYTL5	ENST00000297875.7	c.489A>G	p.Ala163=	synonymous_variant	5/17	5	NM_138780.3	P4
SYTL5	ENST00000456733.2	c.489A>G	p.Ala163=	synonymous_variant	4/17	1		A1

Frequencies

GnomAD3 genomes AF: 0.292 AC: 32276 AN: 110620 Hom.: 3865 Cov.: 22 AF XY: 0.280 AC XY: 9199 AN XY: 32910

Gnomad AFR AF: 0.416

Gnomad AMI AF: 0.214

Gnomad AMR AF: 0.345

Gnomad ASJ AF: 0.235

Gnomad EAS AF: 0.0951

Gnomad SAS AF: 0.368

Gnomad FIN AF: 0.123

Gnomad MID AF: 0.310

Gnomad NFE AF: 0.242

Gnomad OTH AF: 0.311

GnomAD3 exomes AF: 0.245 AC: 38576 AN: 157759 Hom.: 4034 AF XY: 0.222 AC XY: 10829 AN XY: 48779

Gnomad AFR exome AF: 0.412

Gnomad AMR exome AF: 0.335

Gnomad ASJ exome AF: 0.218

Gnomad EAS exome AF: 0.0939

Gnomad SAS exome AF: 0.347

Gnomad FIN exome AF: 0.127

Gnomad NFE exome AF: 0.217

Gnomad OTH exome AF: 0.265

GnomAD4 exome AF: 0.248 AC: 269093 AN: 1084491 Hom.: 23614 Cov.: 29 AF XY: 0.249 AC XY: 88308 AN XY: 354113

Gnomad4 AFR exome AF: 0.436

Gnomad4 AMR exome AF: 0.338

Gnomad4 ASJ exome AF: 0.222

Gnomad4 EAS exome AF: 0.109

Gnomad4 SAS exome AF: 0.351

Gnomad4 FIN exome AF: 0.139

Gnomad4 NFE exome AF: 0.242

Gnomad4 OTH exome AF: 0.269

GnomAD4 genome AF: 0.292 AC: 32294 AN: 110677 Hom.: 3865 Cov.: 22 AF XY: 0.280 AC XY: 9223 AN XY: 32977

Gnomad4 AFR AF: 0.416

Gnomad4 AMR AF: 0.345

Gnomad4 ASJ AF: 0.235

Gnomad4 EAS AF: 0.0945

Gnomad4 SAS AF: 0.368

Gnomad4 FIN AF: 0.123

Gnomad4 NFE AF: 0.242

Gnomad4 OTH AF: 0.307

Alfa AF: 0.268 Hom.: 4807

Bravo AF: 0.316

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	1.1
Dann	Benign	0.48

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs4827330; hg19: chrX-37932886; COSMIC: COSV52901394;