Genetic Variant SYT8:p.Ser117Asn (chr11-1835977-G-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001394072.1(SYT8):c.350G>A(p.Ser117Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000523 in 1,606,064 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 34)

Exomes 𝑓: 0.000052 ( 0 hom. )

Consequence

SYT8
NM_001394072.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.923

Publications

0 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.032291025).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001394072.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SYT8	NM_001394072.1	MANE Select	c.350G>A	p.Ser117Asn	missense	Exon 3 of 8	NP_001381001.1	Q8NBV8-4
SYT8	NM_001290332.2		c.395G>A	p.Ser132Asn	missense	Exon 4 of 9	NP_001277261.2
SYT8	NM_001290333.2		c.392G>A	p.Ser131Asn	missense	Exon 4 of 9	NP_001277262.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SYT8	ENST00000341958.4	TSL:5 MANE Select	c.350G>A	p.Ser117Asn	missense	Exon 3 of 8	ENSP00000343691.3	Q8NBV8-4
SYT8	ENST00000381978.7	TSL:1	c.386G>A	p.Ser129Asn	missense	Exon 4 of 9	ENSP00000371406.3	H0Y3G9
SYT8	ENST00000490707.5	TSL:1	n.2186G>A		non_coding_transcript_exon	Exon 1 of 3

Frequencies

GnomAD3 genomes

AF:

0.0000591

AC:

AN:

152252

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000132

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000413

AC:

AN:

242168

AF XY:

0.0000380

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000816

Gnomad OTH exome

AF:

0.000171

GnomAD4 exome

AF:

0.0000516

AC:

AN:

1453694

Hom.:

Cov.:

AF XY:

0.0000511

AC XY:

AN XY:

723428

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32978

American (AMR)

AF:

0.00

AC:

AN:

42024

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25730

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39666

South Asian (SAS)

AF:

0.00

AC:

AN:

85336

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52558

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5724

European-Non Finnish (NFE)

AF:

0.0000631

AC:

AN:

1109650

Other (OTH)

AF:

0.0000666

AC:

AN:

60028

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000591

AC:

AN:

152370

Hom.:

Cov.:

AF XY:

0.0000537

AC XY:

AN XY:

74514

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41586

American (AMR)

AF:

0.00

AC:

AN:

15312

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10630

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000132

AC:

AN:

68038

Other (OTH)

AF:

0.00

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000378

ExAC

AF:

0.0000330

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.000178

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.47

CADD

Benign

(source)

DANN

Benign

0.84

DEOGEN2

Benign

0.0079

Eigen

Benign

-0.94

Eigen_PC

Benign

-0.95

FATHMM_MKL

Benign

0.026

LIST_S2

Benign

0.48

M_CAP

Benign

0.0045

MetaRNN

Benign

0.032

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.2

PhyloP100

0.92

PrimateAI

Uncertain

0.56

PROVEAN

Benign

-0.88

REVEL

Benign

0.024

Sift

Benign

0.43

Sift4G

Benign

0.22

Polyphen

0.031

Vest4

0.14

MVP

0.15

MPC

0.071

ClinPred

0.029

GERP RS

0.93

Varity_R

0.13

gMVP

0.18

Mutation Taster

=95/5

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over