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GeneBe

12-33426278-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_198992.4(SYT10):c.369C>T(p.Ala123=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00451 in 1,613,978 control chromosomes in the GnomAD database, including 309 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.025 ( 182 hom., cov: 32)
Exomes 𝑓: 0.0024 ( 127 hom. )

Consequence

SYT10
NM_198992.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.83
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.8).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 12-33426278-G-A is Benign according to our data. Variant chr12-33426278-G-A is described in ClinVar as [Benign]. Clinvar id is 768537.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-2.84 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0851 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SYT10NM_198992.4 linkuse as main transcriptc.369C>T p.Ala123= synonymous_variant 2/7 ENST00000228567.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SYT10ENST00000228567.7 linkuse as main transcriptc.369C>T p.Ala123= synonymous_variant 2/71 NM_198992.4 P1
SYT10ENST00000539102.1 linkuse as main transcriptc.369C>T p.Ala123= synonymous_variant, NMD_transcript_variant 2/91

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0249
AC:
3791
AN:
152030
Hom.:
182
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0874
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00761
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000192
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00633
Gnomad NFE
AF:
0.000353
Gnomad OTH
AF:
0.0153
GnomAD3 exomes
AF:
0.00653
AC:
1642
AN:
251422
Hom.:
79
AF XY:
0.00484
AC XY:
658
AN XY:
135882
show subpopulations
Gnomad AFR exome
AF:
0.0906
Gnomad AMR exome
AF:
0.00356
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000163
Gnomad SAS exome
AF:
0.000261
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000193
Gnomad OTH exome
AF:
0.00228
GnomAD4 exome
AF:
0.00238
AC:
3478
AN:
1461830
Hom.:
127
Cov.:
32
AF XY:
0.00207
AC XY:
1505
AN XY:
727212
show subpopulations
Gnomad4 AFR exome
AF:
0.0838
Gnomad4 AMR exome
AF:
0.00432
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000176
Gnomad4 SAS exome
AF:
0.000197
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000113
Gnomad4 OTH exome
AF:
0.00505
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0250
AC:
3808
AN:
152148
Hom.:
182
Cov.:
32
AF XY:
0.0240
AC XY:
1785
AN XY:
74366
show subpopulations
Gnomad4 AFR
AF:
0.0875
Gnomad4 AMR
AF:
0.00760
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.000208
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000353
Gnomad4 OTH
AF:
0.0152
Alfa
AF:
0.0112
Hom.:
35
Bravo
AF:
0.0280
Asia WGS
AF:
0.00433
AC:
15
AN:
3478
EpiCase
AF:
0.000164
EpiControl
AF:
0.000119

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 submitterclinical testingInvitaeDec 31, 2019- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.80
Cadd
Benign
3.8
Dann
Benign
0.27

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: rs11832759; hg19: chr12-33579213; COSMIC: COSV57340852; COSMIC: COSV57340852; API