Variant 12-33382460-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_198992.4(SYT10):c.1259C>G(p.Thr420Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000592 in 1,612,990 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.0034 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00030 ( 6 hom. )

Consequence

SYT10
NM_198992.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 9.24

Variant links:

Genes affected

SYT10 (HGNC:19266): (synaptotagmin 10) Predicted to enable several functions, including phospholipid binding activity; protein dimerization activity; and syntaxin binding activity. Predicted to be involved in several processes, including cellular response to calcium ion; regulation of secretion by cell; and sensory perception of smell. Predicted to be located in synapse and transport vesicle membrane. Predicted to be integral component of membrane. Predicted to be active in exocytic vesicle and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

SYT10 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008290082).

BP6

Variant 12-33382460-G-C is Benign according to our data. Variant chr12-33382460-G-C is described in ClinVar as [Benign]. Clinvar id is 714177.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SYT10	NM_198992.4 linkuse as main transcript	c.1259C>G	p.Thr420Ser	missense_variant	5/7	ENST00000228567.7
SYT10	XM_011520644.4 linkuse as main transcript	c.716C>G	p.Thr239Ser	missense_variant	4/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SYT10	ENST00000228567.7 linkuse as main transcript	c.1259C>G	p.Thr420Ser	missense_variant	5/7	1	NM_198992.4	P1
SYT10	ENST00000539102.1 linkuse as main transcript	c.*854C>G		3_prime_UTR_variant, NMD_transcript_variant	7/9	1

Frequencies

GnomAD3 genomes

AF:

0.00337

AC:

512

AN:

152142

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0117

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00124

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:

0.0000147

Gnomad OTH

AF:

0.00334

GnomAD3 exomes

AF:

0.000783

AC:

196

AN:

250442

Hom.:

AF XY:

0.000606

AC XY:

AN XY:

135394

show subpopulations

Gnomad AFR exome

AF:

0.0101

Gnomad AMR exome

AF:

0.000818

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.000329

GnomAD4 exome

AF:

0.000299

AC:

437

AN:

1460730

Hom.:

Cov.:

AF XY:

0.000227

AC XY:

165

AN XY:

726684

show subpopulations

Gnomad4 AFR exome

AF:

0.0104

Gnomad4 AMR exome

AF:

0.000875

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.000779

GnomAD4 genome

AF:

0.00340

AC:

518

AN:

152260

Hom.:

Cov.:

AF XY:

0.00324

AC XY:

241

AN XY:

74430

show subpopulations

Gnomad4 AFR

AF:

0.0118

Gnomad4 AMR

AF:

0.00124

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.000475

Hom.:

Bravo

AF:

0.00332

ESP6500AA

AF:

0.00953

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000988

AC:

120

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

May 17, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.27

Cadd

Benign

Dann

Benign

0.92

DEOGEN2

Benign

0.078

Eigen

Benign

-0.35

Eigen_PC

Benign

-0.12

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.78

MetaRNN

Benign

0.0083

MetaSVM

Benign

-0.99

MutationAssessor

Benign

-0.36

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.77

PROVEAN

Benign

0.15

REVEL

Benign

0.27

Sift

Benign

0.89

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.20

MutPred

0.20

Gain of catalytic residue at K422 (P = 0.0183);

MVP

0.61

MPC

0.15

ClinPred

0.065

GERP RS

4.0

Varity_R

0.11

gMVP

0.21

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over