rs12799959

Positions:

• chr11-7299304-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_175733.4(SYT9):​c.146-3735C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.263 in 151,942 control chromosomes in the GnomAD database, including 6,021 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.26 (6021 hom., cov: 32)
• Consequence: SYT9 NM_175733.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.257

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.373 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SYT9	NM_175733.4	c.146-3735C>A		intron_variant		ENST00000318881.11	NP_783860.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SYT9	ENST00000318881.11	c.146-3735C>A		intron_variant		1	NM_175733.4	ENSP00000324419	P1
SYT9	ENST00000524820.6	c.50-3735C>A		intron_variant, NMD_transcript_variant		2		ENSP00000432141
SYT9	ENST00000532592.1	c.146-3735C>A		intron_variant, NMD_transcript_variant		2		ENSP00000434558

Frequencies

GnomAD3 genomes AF: 0.264 AC: 40025 AN: 151824 Hom.: 6026 Cov.: 32

Gnomad AFR AF: 0.126

Gnomad AMI AF: 0.422

Gnomad AMR AF: 0.308

Gnomad ASJ AF: 0.297

Gnomad EAS AF: 0.0810

Gnomad SAS AF: 0.387

Gnomad FIN AF: 0.340

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.327

Gnomad OTH AF: 0.271

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.263 AC: 40035 AN: 151942 Hom.: 6021 Cov.: 32 AF XY: 0.264 AC XY: 19625 AN XY: 74266

Gnomad4 AFR AF: 0.126

Gnomad4 AMR AF: 0.308

Gnomad4 ASJ AF: 0.297

Gnomad4 EAS AF: 0.0810

Gnomad4 SAS AF: 0.387

Gnomad4 FIN AF: 0.340

Gnomad4 NFE AF: 0.326

Gnomad4 OTH AF: 0.268

Alfa AF: 0.320 Hom.: 9188

Bravo AF: 0.250

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.1
DANN	Benign	0.67

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

Other links and lift over

dbSNP: rs12799959; hg19: chr11-7320535;