Genetic Variant SYT14:c.61+13176A>G (chr1-209965932-A-G) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001146261.4(SYT14):c.115A>G(p.Thr39Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000594 in 454,224 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000073 ( 0 hom. )

Consequence

SYT14
NM_001146261.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.863

Publications

0 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: Unknown, AR Classification: SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia, Orphanet

SYT14 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.027591199).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001146261.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SYT14	NM_001146262.4	MANE Select	c.61+13176A>G		intron	N/A	NP_001139734.1	Q8NB59-6
SYT14	NM_001146261.4		c.115A>G	p.Thr39Ala	missense	Exon 3 of 10	NP_001139733.1	Q8NB59-7
SYT14	NM_001146264.4		c.115A>G	p.Thr39Ala	missense	Exon 3 of 9	NP_001139736.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SYT14	ENST00000367019.6	TSL:1 MANE Select	c.61+13176A>G	intron	N/A	ENSP00000355986.1	Q8NB59-6
SYT14	ENST00000472886.5	TSL:1	c.61+13176A>G	intron	N/A	ENSP00000418901.1	Q8NB59-1
SYT14	ENST00000367015.5	TSL:1	c.-54+12673A>G	intron	N/A	ENSP00000355982.1	Q8NB59-3

Frequencies

GnomAD3 genomes

AF:

0.0000331

AC:

AN:

151020

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000733

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000419

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000463

AC:

AN:

129706

AF XY:

0.0000422

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000726

AC:

AN:

303090

Hom.:

Cov.:

AF XY:

0.000104

AC XY:

AN XY:

172680

show subpopulations

African (AFR)

AF:

0.000234

AC:

AN:

8552

American (AMR)

AF:

0.00

AC:

AN:

27206

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

10760

East Asian (EAS)

AF:

0.00

AC:

AN:

9202

South Asian (SAS)

AF:

0.000235

AC:

AN:

59624

European-Finnish (FIN)

AF:

0.00

AC:

AN:

12464

Middle Eastern (MID)

AF:

0.000387

AC:

AN:

2582

European-Non Finnish (NFE)

AF:

0.00000631

AC:

AN:

158540

Other (OTH)

AF:

0.000282

AC:

AN:

14160

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.461

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:

0.0000331

AC:

AN:

151134

Hom.:

Cov.:

AF XY:

0.0000542

AC XY:

AN XY:

73744

show subpopulations

African (AFR)

AF:

0.0000974

AC:

AN:

41054

American (AMR)

AF:

0.00

AC:

AN:

15170

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5144

South Asian (SAS)

AF:

0.000209

AC:

AN:

4774

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10372

Middle Eastern (MID)

AF:

0.00

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67854

Other (OTH)

AF:

0.00

AC:

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

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:

0.00

Hom.:

Bravo

AF:

0.0000113

Asia WGS

AF:

0.00173

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.063

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.86

(source)

DANN

Benign

0.15

Eigen

Benign

-1.9

Eigen_PC

Benign

-2.0

FATHMM_MKL

Benign

0.000040

LIST_S2

Benign

0.047

M_CAP

Benign

0.0021

MetaRNN

Benign

0.028

MetaSVM

Benign

-0.96

PhyloP100

-0.86

PrimateAI

Benign

0.43

Sift4G

Benign

0.27

Vest4

0.090

MVP

0.043

ClinPred

0.0096

GERP RS

0.13

gMVP

0.15

Mutation Taster

=99/1

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over