chr1-209965932-A-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001146262.4(SYT14):​c.61+13176A>G variant causes a intron 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. 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_001146262.4 intron

Scores

13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.863
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.027591199).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SYT14NM_001146262.4 linkuse as main transcriptc.61+13176A>G intron_variant ENST00000367019.6 NP_001139734.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SYT14ENST00000367019.6 linkuse as main transcriptc.61+13176A>G intron_variant 1 NM_001146262.4 ENSP00000355986 Q8NB59-6

Frequencies

GnomAD3 genomes
AF:
0.0000331
AC:
5
AN:
151020
Hom.:
0
Cov.:
31
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
GnomAD3 exomes
AF:
0.0000463
AC:
6
AN:
129706
Hom.:
0
AF XY:
0.0000422
AC XY:
3
AN XY:
71080
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 SAS exome
AF:
0.000270
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000726
AC:
22
AN:
303090
Hom.:
0
Cov.:
0
AF XY:
0.000104
AC XY:
18
AN XY:
172680
show subpopulations
Gnomad4 AFR exome
AF:
0.000234
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000235
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000631
Gnomad4 OTH exome
AF:
0.000282
GnomAD4 genome
AF:
0.0000331
AC:
5
AN:
151134
Hom.:
0
Cov.:
31
AF XY:
0.0000542
AC XY:
4
AN XY:
73744
show subpopulations
Gnomad4 AFR
AF:
0.0000974
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000209
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000113
Asia WGS
AF:
0.00173
AC:
6
AN:
3478

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAthena DiagnosticsJan 08, 2021- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
-0.59
T
BayesDel_noAF
Benign
-0.80
CADD
Benign
0.86
DANN
Benign
0.15
Eigen
Benign
-1.9
Eigen_PC
Benign
-2.0
FATHMM_MKL
Benign
0.000040
N
LIST_S2
Benign
0.047
T
M_CAP
Benign
0.0021
T
MetaRNN
Benign
0.028
T
MetaSVM
Benign
-0.96
T
MutationTaster
Benign
1.0
N;N;N;N;N;N;N
PrimateAI
Benign
0.43
T
Sift4G
Benign
0.27
T
Vest4
0.090
MVP
0.043
ClinPred
0.0096
T
GERP RS
0.13
gMVP
0.15

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.

Other links and lift over

dbSNP: rs866440102; hg19: chr1-210139277; API