rs147636620

Variant names:

• chr11-7303252-C-A
• NM_175733.4:c.359C>A

Your query was ambiguous. Multiple possible variants found:

• chr11-7303252-C-A
• chr11-7303252-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_175733.4(SYT9):​c.359C>A​(p.Thr120Lys) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,794 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T120M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SYT9 NM_175733.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.87

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]

ACMG classification

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=0.09557766).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYT9	NM_175733.4	c.359C>A	p.Thr120Lys	missense_variant	Exon 2 of 7	ENST00000318881.11	NP_783860.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYT9	ENST00000318881.11	c.359C>A	p.Thr120Lys	missense_variant	Exon 2 of 7	1	NM_175733.4	ENSP00000324419.6
SYT9	ENST00000524820.6	n.263C>A		non_coding_transcript_exon_variant	Exon 2 of 9	2		ENSP00000432141.2
SYT9	ENST00000532592.1	n.359C>A		non_coding_transcript_exon_variant	Exon 2 of 6	2		ENSP00000434558.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461794 Hom.: 0 Cov.: 36 AF XY: 0.00 AC XY: 0 AN XY: 727206

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.076	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	19
DANN	Benign	0.95
DEOGEN2	Benign	0.0097	T
Eigen	Benign	-0.15
Eigen_PC	Benign	-0.011
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.096	T
MetaSVM	Benign	-0.82	T
MutationAssessor	Benign	1.5	L
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.90	N
REVEL	Benign	0.10
Sift	Benign	0.23	T
Sift4G	Benign	0.31	T
Polyphen		0.0090	B
Vest4		0.28
MutPred		0.29		Gain of ubiquitination at T120 (P = 0.0031);
MVP		0.60
MPC		0.53
ClinPred		0.51	D
GERP RS		4.8
Varity_R		0.20
gMVP		0.38

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: chr11-7324483;