6-158760708-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_001242394.2(SYTL3):c.1377C>T(p.Leu459=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00496 in 1,614,144 control chromosomes in the GnomAD database, including 26 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0035 (3 hom., cov: 32)
  • Exomes 𝑓: 0.0051 (23 hom.)
• Consequence: SYTL3 NM_001242394.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.707

Genes affected

SYTL3 (HGNC:15587): (synaptotagmin like 3) The protein encoded by this gene belongs to a family of peripheral membrane proteins that play a role in vesicular trafficking. This protein binds phospholipids in the presence of calcium ions. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2016]

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BP6: Variant 6-158760708-C-T is Benign according to our data. Variant chr6-158760708-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2657092.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.707 with no splicing effect.
• BS2: High Homozygotes in GnomAd at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SYTL3	NM_001242394.2	c.1377C>T	p.Leu459=	synonymous_variant	15/18	ENST00000611299.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SYTL3	ENST00000611299.5	c.1377C>T	p.Leu459=	synonymous_variant	15/18	5	NM_001242394.2	P1
SYTL3	ENST00000360448.8	c.1377C>T	p.Leu459=	synonymous_variant	16/19	5		P1
SYTL3	ENST00000367081.7	c.1173C>T	p.Leu391=	synonymous_variant	13/16	5

Frequencies

GnomAD3 genomes AF: 0.00350 AC: 532 AN: 152196 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.00181

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00118

Gnomad ASJ AF: 0.00403

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00248

Gnomad FIN AF: 0.00395

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00534

Gnomad OTH AF: 0.00382

GnomAD3 exomes AF: 0.00352 AC: 886 AN: 251476 Hom.: 1 AF XY: 0.00358 AC XY: 486 AN XY: 135916

Gnomad AFR exome AF: 0.00221

Gnomad AMR exome AF: 0.00168

Gnomad ASJ exome AF: 0.00367

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000817

Gnomad FIN exome AF: 0.00379

Gnomad NFE exome AF: 0.00550

Gnomad OTH exome AF: 0.00358

GnomAD4 exome AF: 0.00511 AC: 7477 AN: 1461830 Hom.: 23 Cov.: 31 AF XY: 0.00500 AC XY: 3636 AN XY: 727222

Gnomad4 AFR exome AF: 0.00161

Gnomad4 AMR exome AF: 0.00163

Gnomad4 ASJ exome AF: 0.00325

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000777

Gnomad4 FIN exome AF: 0.00346

Gnomad4 NFE exome AF: 0.00606

Gnomad4 OTH exome AF: 0.00444

GnomAD4 genome AF: 0.00349 AC: 532 AN: 152314 Hom.: 3 Cov.: 32 AF XY: 0.00317 AC XY: 236 AN XY: 74482

Gnomad4 AFR AF: 0.00180

Gnomad4 AMR AF: 0.00118

Gnomad4 ASJ AF: 0.00403

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00248

Gnomad4 FIN AF: 0.00395

Gnomad4 NFE AF: 0.00534

Gnomad4 OTH AF: 0.00378

Alfa AF: 0.00467 Hom.: 1

Bravo AF: 0.00334

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00513

EpiControl AF: 0.00480

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Apr 01, 2023

SYTL3: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
Cadd	Benign	0.67
Dann	Benign	0.78

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: rs117895837; hg19: chr6-159181740; COSMIC: COSV99792827; COSMIC: COSV99792827;