Genetic Variant NM_001394072.1:c.479C>T (chr11-1836247-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001394072.1(SYT8):c.479C>T(p.Thr160Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000417 in 1,580,898 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 34)

Exomes 𝑓: 0.000039 ( 0 hom. )

Consequence

SYT8
NM_001394072.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.89

Publications

1 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (MetaRNN=0.21334553).

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.479C>T	p.Thr160Met	missense	Exon 4 of 8	NP_001381001.1	Q8NBV8-4
SYT8	NM_001290332.2		c.524C>T	p.Thr175Met	missense	Exon 5 of 9	NP_001277261.2
SYT8	NM_001290333.2		c.521C>T	p.Thr174Met	missense	Exon 5 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.479C>T	p.Thr160Met	missense	Exon 4 of 8	ENSP00000343691.3	Q8NBV8-4
SYT8	ENST00000381978.7	TSL:1	c.515C>T	p.Thr172Met	missense	Exon 5 of 9	ENSP00000371406.3	H0Y3G9
SYT8	ENST00000490707.5	TSL:1	n.2456C>T		non_coding_transcript_exon	Exon 1 of 3

Frequencies

GnomAD3 genomes

AF:

0.0000591

AC:

AN:

152176

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.0000873

AC:

AN:

206150

AF XY:

0.0000984

show subpopulations

Gnomad AFR exome

AF:

0.0000689

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:

0.0000880

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000392

AC:

AN:

1428604

Hom.:

Cov.:

AF XY:

0.0000550

AC XY:

AN XY:

708840

show subpopulations

African (AFR)

AF:

0.0000310

AC:

AN:

32286

American (AMR)

AF:

0.00

AC:

AN:

39710

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23886

East Asian (EAS)

AF:

0.00

AC:

AN:

39114

South Asian (SAS)

AF:

0.000248

AC:

AN:

80640

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50790

Middle Eastern (MID)

AF:

0.000178

AC:

AN:

5616

European-Non Finnish (NFE)

AF:

0.0000292

AC:

AN:

1097660

Other (OTH)

AF:

0.0000340

AC:

AN:

58902

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

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:

0.0000657

AC:

AN:

152294

Hom.:

Cov.:

AF XY:

0.0000806

AC XY:

AN XY:

74462

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41554

American (AMR)

AF:

0.00

AC:

AN:

15312

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.000622

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10608

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000735

AC:

AN:

68028

Other (OTH)

AF:

0.000473

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

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:

0.000115

Hom.:

Bravo

AF:

0.0000340

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000746

AC:

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

0.14

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.34

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.33

Eigen

Benign

0.091

Eigen_PC

Benign

-0.14

FATHMM_MKL

Benign

0.26

LIST_S2

Benign

0.74

M_CAP

Benign

0.030

MetaRNN

Benign

0.21

MetaSVM

Benign

-1.0

MutationAssessor

Pathogenic

3.1

PhyloP100

1.9

PrimateAI

Uncertain

0.53

PROVEAN

Pathogenic

-5.1

REVEL

Benign

0.11

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0010

Polyphen

1.0

Vest4

0.43

MVP

0.33

MPC

0.38

ClinPred

0.60

GERP RS

2.8

Varity_R

0.27

gMVP

0.71

Mutation Taster

=74/26

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