Variant chr11-85725457-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_206927.4(SYTL2):c.3901A>G(p.Met1301Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.661 in 1,613,818 control chromosomes in the GnomAD database, including 355,306 homozygotes. In-silico tool predicts a benign outcome for this variant. 10/13 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.70 ( 38235 hom., cov: 32)

Exomes 𝑓: 0.66 ( 317071 hom. )

Consequence

SYTL2
NM_206927.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.78

Variant links:

Genes affected

SYTL2 (HGNC:15585): (synaptotagmin like 2) The protein encoded by this gene is a synaptotagmin-like protein (SLP) that belongs to a C2 domain-containing protein family. The SLP homology domain (SHD) of this protein has been shown to specifically bind the GTP-bound form of Ras-related protein Rab-27A (RAB27A). This protein plays a role in RAB27A-dependent vesicle trafficking and controls melanosome distribution in the cell periphery. Alternative splicing results in multiple transcript variants encoding distinct isoforms.[provided by RefSeq, Jun 2009]

SYTL2 links:

SYTL2 (HGNC:):

SYTL2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=8.3917257E-7).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.825 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SYTL2	NM_206927.4 linkuse as main transcript	c.3901A>G	p.Met1301Val	missense_variant	8/20	ENST00000359152.10	NP_996810.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SYTL2	ENST00000359152.10 linkuse as main transcript	c.3901A>G	p.Met1301Val	missense_variant	8/20	1	NM_206927.4	ENSP00000352065.7		A0A8J9FM55

Frequencies

GnomAD3 genomes

AF:

0.703

AC:

106884

AN:

151984

Hom.:

38204

Cov.:

show subpopulations

Gnomad AFR

AF:

0.832

Gnomad AMI

AF:

0.532

Gnomad AMR

AF:

0.627

Gnomad ASJ

AF:

0.668

Gnomad EAS

AF:

0.591

Gnomad SAS

AF:

0.537

Gnomad FIN

AF:

0.718

Gnomad MID

AF:

0.659

Gnomad NFE

AF:

0.665

Gnomad OTH

AF:

0.668

GnomAD3 exomes

AF:

0.648

AC:

162772

AN:

251148

Hom.:

53618

AF XY:

0.643

AC XY:

87268

AN XY:

135746

show subpopulations

Gnomad AFR exome

AF:

0.836

Gnomad AMR exome

AF:

0.573

Gnomad ASJ exome

AF:

0.663

Gnomad EAS exome

AF:

0.605

Gnomad SAS exome

AF:

0.544

Gnomad FIN exome

AF:

0.712

Gnomad NFE exome

AF:

0.666

Gnomad OTH exome

AF:

0.633

GnomAD4 exome

AF:

0.656

AC:

959141

AN:

1461716

Hom.:

317071

Cov.:

AF XY:

0.652

AC XY:

474335

AN XY:

727168

show subpopulations

Gnomad4 AFR exome

AF:

0.840

Gnomad4 AMR exome

AF:

0.576

Gnomad4 ASJ exome

AF:

0.664

Gnomad4 EAS exome

AF:

0.582

Gnomad4 SAS exome

AF:

0.548

Gnomad4 FIN exome

AF:

0.708

Gnomad4 NFE exome

AF:

0.662

Gnomad4 OTH exome

AF:

0.658

GnomAD4 genome

AF:

0.703

AC:

106967

AN:

152102

Hom.:

38235

Cov.:

AF XY:

0.703

AC XY:

52242

AN XY:

74336

show subpopulations

Gnomad4 AFR

AF:

0.832

Gnomad4 AMR

AF:

0.627

Gnomad4 ASJ

AF:

0.668

Gnomad4 EAS

AF:

0.590

Gnomad4 SAS

AF:

0.536

Gnomad4 FIN

AF:

0.718

Gnomad4 NFE

AF:

0.665

Gnomad4 OTH

AF:

0.667

Alfa

AF:

0.663

Hom.:

82906

Bravo

AF:

0.699

TwinsUK

AF:

0.667

AC:

2473

ALSPAC

AF:

0.677

AC:

2608

ESP6500AA

AF:

0.824

AC:

3631

ESP6500EA

AF:

0.657

AC:

5650

ExAC

AF:

0.654

AC:

79459

Asia WGS

AF:

0.572

AC:

1985

AN:

3478

EpiCase

AF:

0.663

EpiControl

AF:

0.647

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.25

DANN

Benign

0.81

Eigen

Benign

-0.87

Eigen_PC

Benign

-0.81

FATHMM_MKL

Benign

0.032

LIST_S2

Benign

0.43

T;T

MetaRNN

Benign

8.4e-7

T;T

MetaSVM

Benign

-1.0

PrimateAI

Benign

0.24

REVEL

Benign

0.016

Sift4G

Benign

0.62

T;T

Vest4

0.048

MPC

0.013

GERP RS

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over