rs973108

chr11-7332943-A-G

Variant summary

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

The NM_175733.4(SYT9):c.1044+19002A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.482 in 152,150 control chromosomes in the GnomAD database, including 18,755 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 0.48 (18755 hom., cov: 33)
• Consequence: SYT9 NM_175733.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.940

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=-0.58).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.571 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SYT9	NM_175733.4	c.1044+19002A>G		intron_variant		ENST00000318881.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SYT9	ENST00000318881.11	c.1044+19002A>G		intron_variant		1	NM_175733.4	P1
SYT9	ENST00000524820.6	c.*141+18606A>G		intron_variant, NMD_transcript_variant		2
SYT9	ENST00000532592.1	c.497+29553A>G		intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.482 AC: 73277 AN: 152034 Hom.: 18761 Cov.: 33

Gnomad AFR AF: 0.363

Gnomad AMI AF: 0.724

Gnomad AMR AF: 0.485

Gnomad ASJ AF: 0.507

Gnomad EAS AF: 0.0846

Gnomad SAS AF: 0.365

Gnomad FIN AF: 0.556

Gnomad MID AF: 0.509

Gnomad NFE AF: 0.576

Gnomad OTH AF: 0.490

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

GnomAD4 genome AF: 0.482 AC: 73289 AN: 152150 Hom.: 18755 Cov.: 33 AF XY: 0.476 AC XY: 35412 AN XY: 74382

Gnomad4 AFR AF: 0.363

Gnomad4 AMR AF: 0.485

Gnomad4 ASJ AF: 0.507

Gnomad4 EAS AF: 0.0847

Gnomad4 SAS AF: 0.366

Gnomad4 FIN AF: 0.556

Gnomad4 NFE AF: 0.576

Gnomad4 OTH AF: 0.483

Alfa AF: 0.548 Hom.: 30348

Bravo AF: 0.469

Asia WGS AF: 0.226 AC: 790 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
Cadd	Benign	6.3
Dann	Benign	0.73

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: rs973108; hg19: chr11-7354174;