Variant rs142853530 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 2P and 12B. PM2BP4_StrongBP6_Very_Strong

The NM_001146262.4(SYT14):c.1055G>A(p.Arg352His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000174 in 1,613,830 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 Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R352C) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00094 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000094 ( 0 hom. )

Consequence

SYT14
NM_001146262.4 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 7.24

Variant links:

Genes affected

SYT14 (HGNC:23143): (synaptotagmin 14) This gene is a member of the synaptotagmin gene family and encodes a protein similar to other family members that mediate membrane trafficking in synaptic transmission. The encoded protein is a calcium-independent synaptotagmin. Mutations in this gene are a cause of autosomal recessive spinocerebellar ataxia-11 (SCAR11), and a t(1;3) translocation of this gene has been associated with neurodevelopmental abnormalities. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene, and a pseudogene of this gene is located on the long arm of chromosome 4. [provided by RefSeq, Dec 2011]

SYT14 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.023833126).

BP6

Variant 1-210100352-G-A is Benign according to our data. Variant chr1-210100352-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 586691.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SYT14	NM_001146262.4 linkuse as main transcript	c.1055G>A	p.Arg352His	missense_variant	6/9	ENST00000367019.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SYT14	ENST00000367019.6 linkuse as main transcript	c.1055G>A	p.Arg352His	missense_variant	6/9	1	NM_001146262.4		Q8NB59-6

Frequencies

GnomAD3 genomes

AF:

0.000940

AC:

143

AN:

152070

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00338

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

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:

0.000479

GnomAD3 exomes

AF:

0.000230

AC:

AN:

248274

Hom.:

AF XY:

0.000149

AC XY:

AN XY:

134566

show subpopulations

Gnomad AFR exome

AF:

0.00323

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000359

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000937

AC:

137

AN:

1461642

Hom.:

Cov.:

AF XY:

0.0000825

AC XY:

AN XY:

727094

show subpopulations

Gnomad4 AFR exome

AF:

0.00281

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000464

Gnomad4 FIN exome

AF:

0.0000188

Gnomad4 NFE exome

AF:

0.0000234

Gnomad4 OTH exome

AF:

0.000182

GnomAD4 genome

AF:

0.000940

AC:

143

AN:

152188

Hom.:

Cov.:

AF XY:

0.00101

AC XY:

AN XY:

74402

show subpopulations

Gnomad4 AFR

AF:

0.00337

Gnomad4 AMR

AF:

0.0000655

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:

0.000474

Alfa

AF:

0.000196

Hom.:

Bravo

AF:

0.00115

ESP6500AA

AF:

0.00431

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000239

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

SYT14-related disorder

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 11, 2022

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Athena Diagnostics

Aug 13, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Uncertain

0.0

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.44

.;.;.;.;T;.

Eigen

Pathogenic

0.93

Eigen_PC

Pathogenic

0.92

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.91

D;D;D;D;D;.

M_CAP

Benign

0.037

MetaRNN

Benign

0.024

T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.8

M;.;.;.;M;.

MutationTaster

Benign

1.0

D;D;D;D;D;D;D

PrimateAI

Uncertain

0.70

PROVEAN

Uncertain

-3.8

D;D;.;.;D;D

REVEL

Uncertain

0.48

Sift

Uncertain

0.0020

D;D;.;.;D;D

Sift4G

Uncertain

0.0040

D;D;.;D;D;D

Polyphen

1.0

D;.;.;.;D;.

Vest4

0.42

MVP

0.28

ClinPred

0.21

GERP RS

6.1

Varity_R

0.51

gMVP

0.48

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