11-7303080-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_175733.4(SYT9):​c.187G>C​(p.Gly63Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

SYT9
NM_175733.4 missense

Scores

11
4
4

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.60
Variant links:
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 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.874

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SYT9NM_175733.4 linkc.187G>C p.Gly63Arg missense_variant 2/7 ENST00000318881.11 NP_783860.1 Q86SS6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SYT9ENST00000318881.11 linkc.187G>C p.Gly63Arg missense_variant 2/71 NM_175733.4 ENSP00000324419.6 Q86SS6
SYT9ENST00000524820.6 linkn.91G>C non_coding_transcript_exon_variant 2/92 ENSP00000432141.2 E9PDN4
SYT9ENST00000532592.1 linkn.187G>C non_coding_transcript_exon_variant 2/62 ENSP00000434558.1 B3KNT7

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
32

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 submitterclinical testingAmbry GeneticsOct 09, 2024The c.187G>C (p.G63R) alteration is located in exon 2 (coding exon 2) of the SYT9 gene. This alteration results from a G to C substitution at nucleotide position 187, causing the glycine (G) at amino acid position 63 to be replaced by an arginine (R). 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
Pathogenic
1.0
BayesDel_addAF
Pathogenic
0.33
D
BayesDel_noAF
Pathogenic
0.24
CADD
Pathogenic
29
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.33
T
Eigen
Pathogenic
0.89
Eigen_PC
Pathogenic
0.90
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.95
D
M_CAP
Benign
0.044
D
MetaRNN
Pathogenic
0.87
D
MetaSVM
Benign
-0.50
T
MutationAssessor
Uncertain
2.9
M
PrimateAI
Pathogenic
0.94
D
PROVEAN
Pathogenic
-4.7
D
REVEL
Uncertain
0.57
Sift
Uncertain
0.0010
D
Sift4G
Pathogenic
0.0010
D
Polyphen
1.0
D
Vest4
0.97
MutPred
0.63
Gain of methylation at G63 (P = 0.0182);
MVP
0.86
MPC
1.4
ClinPred
1.0
D
GERP RS
5.9
Varity_R
0.80
gMVP
0.79

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-7324311; API