X-38108615-T-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_138780.3(SYTL5):c.1350T>C(p.Tyr450=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.27 in 1,185,999 control chromosomes in the GnomAD database, including 36,927 homozygotes. There are 101,193 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 0.39 (8631 hom., 12203 hem., cov: 22)
  • Exomes 𝑓: 0.26 (28296 hom. 88990 hem.)
• Consequence: SYTL5 NM_138780.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.288

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BP6: Variant X-38108615-T-C is Benign according to our data. Variant chrX-38108615-T-C is described in Lovd as [Likely_benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.761 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SYTL5	NM_138780.3	c.1350T>C	p.Tyr450=	synonymous_variant	12/17	ENST00000297875.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SYTL5	ENST00000297875.7	c.1350T>C	p.Tyr450=	synonymous_variant	12/17	5	NM_138780.3	P4
SYTL5	ENST00000456733.2	c.1416T>C	p.Tyr472=	synonymous_variant	12/17	1		A1

Frequencies

GnomAD3 genomes AF: 0.392 AC: 43370 AN: 110521 Hom.: 8627 Cov.: 22 AF XY: 0.371 AC XY: 12161 AN XY: 32783

Gnomad AFR AF: 0.769

Gnomad AMI AF: 0.218

Gnomad AMR AF: 0.382

Gnomad ASJ AF: 0.235

Gnomad EAS AF: 0.101

Gnomad SAS AF: 0.362

Gnomad FIN AF: 0.124

Gnomad MID AF: 0.325

Gnomad NFE AF: 0.242

Gnomad OTH AF: 0.386

GnomAD3 exomes AF: 0.291 AC: 47191 AN: 162033 Hom.: 6473 AF XY: 0.280 AC XY: 14489 AN XY: 51753

Gnomad AFR exome AF: 0.785

Gnomad AMR exome AF: 0.372

Gnomad ASJ exome AF: 0.227

Gnomad EAS exome AF: 0.104

Gnomad SAS exome AF: 0.357

Gnomad FIN exome AF: 0.132

Gnomad NFE exome AF: 0.237

Gnomad OTH exome AF: 0.288

GnomAD4 exome AF: 0.258 AC: 277128 AN: 1075425 Hom.: 28296 Cov.: 26 AF XY: 0.256 AC XY: 88990 AN XY: 347827

Gnomad4 AFR exome AF: 0.791

Gnomad4 AMR exome AF: 0.370

Gnomad4 ASJ exome AF: 0.223

Gnomad4 EAS exome AF: 0.112

Gnomad4 SAS exome AF: 0.348

Gnomad4 FIN exome AF: 0.140

Gnomad4 NFE exome AF: 0.240

Gnomad4 OTH exome AF: 0.291

GnomAD4 genome AF: 0.393 AC: 43411 AN: 110574 Hom.: 8631 Cov.: 22 AF XY: 0.372 AC XY: 12203 AN XY: 32846

Gnomad4 AFR AF: 0.769

Gnomad4 AMR AF: 0.382

Gnomad4 ASJ AF: 0.235

Gnomad4 EAS AF: 0.100

Gnomad4 SAS AF: 0.363

Gnomad4 FIN AF: 0.124

Gnomad4 NFE AF: 0.242

Gnomad4 OTH AF: 0.382

Alfa AF: 0.323 Hom.: 4740

Bravo AF: 0.431

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
Cadd	Benign	5.5
Dann	Benign	0.71

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: rs5918476; hg19: chrX-37967868; COSMIC: COSV52901409;