rs149170280

Variant names:

Variant summary

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

The NM_001146262.4(SYT14):c.202A>G(p.Arg68Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000778 in 1,612,266 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.00041 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00082 ( 1 hom. )

Consequence

SYT14
NM_001146262.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:3

Conservation

PhyloP100: 5.23

Publications

2 publications found

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 Gene-Disease associations (from GenCC):

autosomal recessive spinocerebellar ataxia 11
Inheritance: AR, Unknown Classification: SUPPORTIVE, LIMITED Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)

SYT14 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=0.06872484).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYT14	NM_001146262.4 link	c.202A>G	p.Arg68Gly	missense_variant	Exon 3 of 9	ENST00000367019.6	NP_001139734.1	Q8NB59-6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYT14	ENST00000367019.6 link	c.202A>G	p.Arg68Gly	missense_variant	Exon 3 of 9	1	NM_001146262.4	ENSP00000355986.1		Q8NB59-6

Frequencies

GnomAD3 genomes

AF:

0.000414

AC:

AN:

152160

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

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:

0.000838

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.000324

AC:

AN:

250216

AF XY:

0.000288

show subpopulations

Gnomad AFR exome

AF:

0.0000627

Gnomad AMR exome

AF:

0.0000580

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000626

Gnomad OTH exome

AF:

0.00115

GnomAD4 exome

AF:

0.000816

AC:

1192

AN:

1460106

Hom.:

Cov.:

AF XY:

0.000756

AC XY:

549

AN XY:

726244

show subpopulations

African (AFR)

AF:

0.000210

AC:

AN:

33400

American (AMR)

AF:

0.000112

AC:

AN:

44608

Ashkenazi Jewish (ASJ)

AF:

0.0000383

AC:

AN:

26090

East Asian (EAS)

AF:

0.00

AC:

AN:

39612

South Asian (SAS)

AF:

0.00

AC:

AN:

85832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53372

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5330

European-Non Finnish (NFE)

AF:

0.000997

AC:

1108

AN:

1111588

Other (OTH)

AF:

0.00118

AC:

AN:

60274

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

112

168

224

280

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

138

184

230

<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:

0.000414

AC:

AN:

152160

Hom.:

Cov.:

AF XY:

0.000336

AC XY:

AN XY:

74330

show subpopulations

African (AFR)

AF:

0.0000724

AC:

AN:

41448

American (AMR)

AF:

0.000131

AC:

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10610

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000838

AC:

AN:

68004

Other (OTH)

AF:

0.000478

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

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:

0.000645

Hom.:

Bravo

AF:

0.000400

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00182

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000698

AC:

ExAC

AF:

0.000288

AC:

EpiCase

AF:

0.00109

EpiControl

AF:

0.000771

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Uncertain:2

Oct 01, 2019

CeGaT Center for Human Genetics Tuebingen

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

May 21, 2024

Athena Diagnostics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Available data are insufficient to determine the clinical significance of the variant at this time. The frequency of this variant in the general population is higher than would generally be expected for pathogenic variants in this gene. (http://gnomad.broadinstitute.org) Polyphen and MutationTaster predict this amino acid change may be benign. -

not specified

Uncertain:1

Sep 09, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.337A>G (p.R113G) alteration is located in exon 4 (coding exon 4) of the SYT14 gene. This alteration results from a A to G substitution at nucleotide position 337, causing the arginine (R) at amino acid position 113 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.086

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.47

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0058

.;.;.;T;.

Eigen

Benign

-0.18

Eigen_PC

Benign

-0.018

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.91

D;D;D;D;.

M_CAP

Benign

0.0039

MetaRNN

Benign

0.069

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.63

N;.;.;N;.

PhyloP100

5.2

PrimateAI

Benign

0.35

PROVEAN

Benign

-0.60

N;N;.;N;N

REVEL

Benign

0.089

Sift

Uncertain

0.018

D;D;.;D;D

Sift4G

Benign

0.35

T;T;T;T;T

Polyphen

0.10

B;.;.;B;.

Vest4

0.36

MVP

0.043

ClinPred

0.042

GERP RS

3.9

Varity_R

0.087

gMVP

0.33

Mutation Taster

=78/22

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over