rs7946495

Positions:

• chr11-7308662-G-A
• chr11-7308662-G-C

Variant summary

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

The NM_175733.4(SYT9):​c.498-4733G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.706 in 151,998 control chromosomes in the GnomAD database, including 37,901 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 0.71 (37901 hom., cov: 31)
• Consequence: SYT9 NM_175733.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.27

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=-0.93).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.752 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SYT9	NM_175733.4	c.498-4733G>A		intron_variant		ENST00000318881.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SYT9	ENST00000318881.11	c.498-4733G>A		intron_variant		1	NM_175733.4	P1
SYT9	ENST00000524820.6	c.402-4733G>A		intron_variant, NMD_transcript_variant		2
SYT9	ENST00000532592.1	c.497+5272G>A		intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.706 AC: 107186 AN: 151882 Hom.: 37884 Cov.: 31

Gnomad AFR AF: 0.686

Gnomad AMI AF: 0.719

Gnomad AMR AF: 0.763

Gnomad ASJ AF: 0.706

Gnomad EAS AF: 0.761

Gnomad SAS AF: 0.672

Gnomad FIN AF: 0.679

Gnomad MID AF: 0.725

Gnomad NFE AF: 0.707

Gnomad OTH AF: 0.710

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

GnomAD4 genome AF: 0.706 AC: 107255 AN: 151998 Hom.: 37901 Cov.: 31 AF XY: 0.705 AC XY: 52383 AN XY: 74302

Gnomad4 AFR AF: 0.686

Gnomad4 AMR AF: 0.763

Gnomad4 ASJ AF: 0.706

Gnomad4 EAS AF: 0.760

Gnomad4 SAS AF: 0.672

Gnomad4 FIN AF: 0.679

Gnomad4 NFE AF: 0.707

Gnomad4 OTH AF: 0.712

Alfa AF: 0.710 Hom.: 77457

Bravo AF: 0.716

Asia WGS AF: 0.739 AC: 2568 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.050
DANN	Benign	0.72

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: rs7946495; hg19: chr11-7329893;