11-7332943-A-G

Variant names:

• chr11-7332943-A-G
• rs973108
• NM_175733.4:c.1044+19002A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
SYT9	NM_175733.4	c.1044+19002A>G		intron_variant	Intron 3 of 6	ENST00000318881.11	NP_783860.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYT9	ENST00000318881.11	c.1044+19002A>G		intron_variant	Intron 3 of 6	1	NM_175733.4	ENSP00000324419.6
SYT9	ENST00000524820.6	n.*141+18606A>G		intron_variant	Intron 4 of 8	2		ENSP00000432141.2
SYT9	ENST00000532592.1	n.497+29553A>G		intron_variant	Intron 2 of 5	2		ENSP00000434558.1

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

African (AFR) AF: 0.363 AC: 15059 AN: 41494

American (AMR) AF: 0.485 AC: 7413 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.507 AC: 1759 AN: 3468

East Asian (EAS) AF: 0.0847 AC: 439 AN: 5186

South Asian (SAS) AF: 0.366 AC: 1764 AN: 4818

European-Finnish (FIN) AF: 0.556 AC: 5890 AN: 10584

Middle Eastern (MID) AF: 0.517 AC: 152 AN: 294

European-Non Finnish (NFE) AF: 0.576 AC: 39131 AN: 67984

Other (OTH) AF: 0.483 AC: 1022 AN: 2114

Alfa AF: 0.540 Hom.: 37768

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
PhyloP100		0.94
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs973108; hg19: chr11-7354174;