Variant rs2292474 details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001394072.1(SYT8):c.1075C>T(p.Arg359Trp) variant causes a missense change. The variant allele was found at a frequency of 0.481 in 1,594,152 control chromosomes in the GnomAD database, including 189,039 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 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 0.42 ( 14671 hom., cov: 35)

Exomes 𝑓: 0.49 ( 174368 hom. )

Consequence

SYT8
NM_001394072.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.09

Variant links:

Genes affected

SYT8 (HGNC:19264): (synaptotagmin 8) This gene encodes a member of the synaptotagmin protein family. Synaptotagmins are membrane proteins that are important in neurotransmission and hormone secretion, both of which involve regulated exocytosis. Expression of the encoded protein in human pancreatic islets has been connected to activity of the promoter for the insulin gene, on the same chromosome several hundred kilobases away (PMID: 21336277 and 22928559). This association would link response to gluclose to insulin secretion. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Mar 2014]

SYT8 links:

SYT8 (HGNC:):

SYT8 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=3.6974954E-5).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.538 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SYT8	NM_001394072.1 linkuse as main transcript	c.1075C>T	p.Arg359Trp	missense_variant	8/8	ENST00000341958.4	NP_001381001.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SYT8	ENST00000341958.4 linkuse as main transcript	c.1075C>T	p.Arg359Trp	missense_variant	8/8	5	NM_001394072.1	ENSP00000343691.3		A6NCR4

Frequencies

GnomAD3 genomes

AF:

0.416

AC:

63225

AN:

152058

Hom.:

14658

Cov.:

show subpopulations

Gnomad AFR

AF:

0.209

Gnomad AMI

AF:

0.601

Gnomad AMR

AF:

0.446

Gnomad ASJ

AF:

0.359

Gnomad EAS

AF:

0.379

Gnomad SAS

AF:

0.554

Gnomad FIN

AF:

0.647

Gnomad MID

AF:

0.405

Gnomad NFE

AF:

0.493

Gnomad OTH

AF:

0.399

GnomAD3 exomes

AF:

0.477

AC:

105701

AN:

221570

Hom.:

25973

AF XY:

0.486

AC XY:

59505

AN XY:

122484

show subpopulations

Gnomad AFR exome

AF:

0.206

Gnomad AMR exome

AF:

0.482

Gnomad ASJ exome

AF:

0.367

Gnomad EAS exome

AF:

0.385

Gnomad SAS exome

AF:

0.557

Gnomad FIN exome

AF:

0.647

Gnomad NFE exome

AF:

0.494

Gnomad OTH exome

AF:

0.481

GnomAD4 exome

AF:

0.488

AC:

703175

AN:

1441976

Hom.:

174368

Cov.:

AF XY:

0.491

AC XY:

352210

AN XY:

717198

show subpopulations

Gnomad4 AFR exome

AF:

0.200

Gnomad4 AMR exome

AF:

0.471

Gnomad4 ASJ exome

AF:

0.357

Gnomad4 EAS exome

AF:

0.388

Gnomad4 SAS exome

AF:

0.557

Gnomad4 FIN exome

AF:

0.637

Gnomad4 NFE exome

AF:

0.494

Gnomad4 OTH exome

AF:

0.461

GnomAD4 genome

AF:

0.416

AC:

63263

AN:

152176

Hom.:

14671

Cov.:

AF XY:

0.426

AC XY:

31661

AN XY:

74400

show subpopulations

Gnomad4 AFR

AF:

0.209

Gnomad4 AMR

AF:

0.446

Gnomad4 ASJ

AF:

0.359

Gnomad4 EAS

AF:

0.380

Gnomad4 SAS

AF:

0.555

Gnomad4 FIN

AF:

0.647

Gnomad4 NFE

AF:

0.493

Gnomad4 OTH

AF:

0.401

Alfa

AF:

0.456

Hom.:

3526

Bravo

AF:

0.390

TwinsUK

AF:

0.482

AC:

1788

ALSPAC

AF:

0.495

AC:

1907

ESP6500AA

AF:

0.208

AC:

906

ESP6500EA

AF:

0.481

AC:

4072

ExAC

AF:

0.467

AC:

55475

Asia WGS

AF:

0.434

AC:

1506

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.021

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Benign

0.91

DEOGEN2

Benign

0.042

T;.

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.21

LIST_S2

Benign

0.69

T;T

MetaRNN

Benign

0.000037

T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

-3.7

N;.

PrimateAI

Uncertain

0.71

PROVEAN

Benign

N;N

REVEL

Benign

0.17

Sift

Benign

1.0

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0

B;B

Vest4

0.10

MPC

0.076

ClinPred

0.0059

GERP RS

2.7

Varity_R

0.068

gMVP

0.64

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

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