Genetic Variant SYT15:p.Thr82Ser (chr10-46580926-C-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate

The NM_031912.5(SYT15):c.245C>G(p.Thr82Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000712 in 140,544 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 7/10 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0000071 ( 0 hom., cov: 23)

Exomes 𝑓: 0.000038 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SYT15
NM_031912.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.84

Publications

0 publications found

Variant links:

Genes affected

SYT15 (HGNC:17167): (synaptotagmin 15) This gene encodes a member of the Synaptotagmin (Syt) family of membrane trafficking proteins. Members of this family contain a transmembrane region and a C-terminal-type tandem C2 domain. Unlike related family members, the encoded protein may be involved in membrane trafficking in non-neuronal tissues. Two trancript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Jul 2008]

SYT15 links:

SYT15-AS1 (HGNC:56167): (SYT15 antisense RNA 1)

SYT15-AS1 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=0.07478407).

BP6

Variant 10-46580926-C-G is Benign according to our data. Variant chr10-46580926-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 3172977.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031912.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYT15	NM_031912.5	MANE Select	c.245C>G	p.Thr82Ser	missense	Exon 3 of 8	NP_114118.2
	SYT15	NM_181519.3		c.245C>G	p.Thr82Ser	missense	Exon 3 of 9	NP_852660.1	Q9BQS2-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SYT15	ENST00000374321.9	TSL:2 MANE Select	c.245C>G	p.Thr82Ser	missense	Exon 3 of 8	ENSP00000363441.4	Q9BQS2-1
SYT15	ENST00000503753.5	TSL:1	c.245C>G	p.Thr82Ser	missense	Exon 3 of 9	ENSP00000427607.1	Q9BQS2-2
SYT15	ENST00000374323.8	TSL:2	c.404C>G	p.Thr135Ser	missense	Exon 2 of 7	ENSP00000363443.3

Frequencies

GnomAD3 genomes

AF:

0.00000712

AC:

AN:

140544

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:

0.0000154

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000805

AC:

AN:

248356

AF XY:

0.0000148

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:

0.0000178

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000384

AC:

AN:

1199084

Hom.:

Cov.:

AF XY:

0.0000373

AC XY:

AN XY:

589178

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

23578

American (AMR)

AF:

0.00

AC:

AN:

26510

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18242

East Asian (EAS)

AF:

0.00

AC:

AN:

36348

South Asian (SAS)

AF:

0.00

AC:

AN:

63832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40064

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4526

European-Non Finnish (NFE)

AF:

0.0000459

AC:

AN:

936150

Other (OTH)

AF:

0.0000602

AC:

AN:

49834

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:

0.00000712

AC:

AN:

140544

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

68338

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

35762

American (AMR)

AF:

0.00

AC:

AN:

14220

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3328

East Asian (EAS)

AF:

0.00

AC:

AN:

4966

South Asian (SAS)

AF:

0.00

AC:

AN:

4354

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9884

Middle Eastern (MID)

AF:

0.00

AC:

AN:

288

European-Non Finnish (NFE)

AF:

0.0000154

AC:

AN:

65010

Other (OTH)

AF:

0.00

AC:

AN:

1898

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

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:

0.0000712

Hom.:

ClinVar

ClinVar submissions

Significance:Likely benign

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

0.063

BayesDel_noAF

Benign

-0.72

CADD

Benign

(source)

DANN

Benign

0.71

DEOGEN2

Benign

0.0030

LIST_S2

Benign

0.39

MetaRNN

Benign

0.075

PhyloP100

1.8

PROVEAN

Benign

-0.070

Sift

Benign

0.84

Sift4G

Benign

1.0

Vest4

0.17

gMVP

0.37

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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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