11-7252196-G-A
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Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The ENST00000318881.11(SYT9):c.10G>A(p.Ala4Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000499 in 1,462,026 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 0.000079 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000047 ( 0 hom. )
Consequence
SYT9
ENST00000318881.11 missense
ENST00000318881.11 missense
Scores
2
1
16
Clinical Significance
Conservation
PhyloP100: 4.58
Genes affected
SYT9 (HGNC:19265): (synaptotagmin 9) Predicted to enable several functions, including calcium ion binding activity; phospholipid binding activity; and syntaxin binding activity. Predicted to be involved in calcium-ion regulated exocytosis; cellular response to calcium ion; and regulation of secretion by cell. Predicted to be located in clathrin-coated endocytic vesicle membrane. Predicted to be active in hippocampal mossy fiber to CA3 synapse; plasma membrane; and secretory vesicle. Predicted to be integral component of synaptic vesicle membrane. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.13416314).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SYT9 | NM_175733.4 | c.10G>A | p.Ala4Thr | missense_variant | 1/7 | ENST00000318881.11 | NP_783860.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SYT9 | ENST00000318881.11 | c.10G>A | p.Ala4Thr | missense_variant | 1/7 | 1 | NM_175733.4 | ENSP00000324419 | P1 | |
SYT9 | ENST00000532592.1 | c.10G>A | p.Ala4Thr | missense_variant, NMD_transcript_variant | 1/6 | 2 | ENSP00000434558 | |||
SYT9 | ENST00000524820.6 | c.49+13280G>A | intron_variant, NMD_transcript_variant | 2 | ENSP00000432141 |
Frequencies
GnomAD3 genomes AF: 0.0000789 AC: 12AN: 152178Hom.: 0 Cov.: 32
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GnomAD4 exome AF: 0.0000466 AC: 61AN: 1309848Hom.: 0 Cov.: 30 AF XY: 0.0000498 AC XY: 32AN XY: 642310
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GnomAD4 genome AF: 0.0000789 AC: 12AN: 152178Hom.: 0 Cov.: 32 AF XY: 0.0000673 AC XY: 5AN XY: 74346
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 25, 2023 | The c.10G>A (p.A4T) alteration is located in exon 1 (coding exon 1) of the SYT9 gene. This alteration results from a G to A substitution at nucleotide position 10, causing the alanine (A) at amino acid position 4 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T
M_CAP
Pathogenic
D
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
N
MutationTaster
Benign
D;D
PrimateAI
Pathogenic
D
PROVEAN
Benign
N
REVEL
Benign
Sift
Benign
T
Sift4G
Benign
T
Polyphen
B
Vest4
MutPred
Loss of loop (P = 0.0128);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at