rs726733

Positions:

• chr11-7309076-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_175733.4(SYT9):​c.498-4319A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00541 in 152,256 control chromosomes in the GnomAD database, including 7 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 0.0054 (7 hom., cov: 32)
• Consequence: SYT9 NM_175733.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0180

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=-0.86).
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00541 (823/152256) while in subpopulation AFR AF= 0.019 (789/41558). AF 95% confidence interval is 0.0179. There are 7 homozygotes in gnomad4. There are 384 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 7 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SYT9	NM_175733.4	c.498-4319A>G		intron_variant		ENST00000318881.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SYT9	ENST00000318881.11	c.498-4319A>G		intron_variant		1	NM_175733.4	P1
SYT9	ENST00000524820.6	c.402-4319A>G		intron_variant, NMD_transcript_variant		2
SYT9	ENST00000532592.1	c.497+5686A>G		intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.00540 AC: 821 AN: 152138 Hom.: 7 Cov.: 32

Gnomad AFR AF: 0.0190

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00144

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00431

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

GnomAD4 genome AF: 0.00541 AC: 823 AN: 152256 Hom.: 7 Cov.: 32 AF XY: 0.00516 AC XY: 384 AN XY: 74456

Gnomad4 AFR AF: 0.0190

Gnomad4 AMR AF: 0.00144

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00426

Alfa AF: 0.00416 Hom.: 1

Bravo AF: 0.00645

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.9
DANN	Benign	0.85

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: rs726733; hg19: chr11-7330307;