11-7262018-G-T

Position:

• chr11-7262018-G-T

Variant summary

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

The NM_175733.4(SYT9):​c.145+9687G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.466 in 151,838 control chromosomes in the GnomAD database, including 16,586 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 0.47 (16586 hom., cov: 31)
• Consequence: SYT9 NM_175733.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.315

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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.514 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SYT9	NM_175733.4	c.145+9687G>T		intron_variant		ENST00000318881.11	NP_783860.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SYT9	ENST00000318881.11	c.145+9687G>T		intron_variant		1	NM_175733.4	ENSP00000324419.6
SYT9	ENST00000524820.6	n.49+23102G>T		intron_variant		2		ENSP00000432141.2
SYT9	ENST00000532592.1	n.145+9687G>T		intron_variant		2		ENSP00000434558.1

Frequencies

GnomAD3 genomes AF: 0.466 AC: 70697 AN: 151720 Hom.: 16559 Cov.: 31

Gnomad AFR AF: 0.519

Gnomad AMI AF: 0.501

Gnomad AMR AF: 0.442

Gnomad ASJ AF: 0.429

Gnomad EAS AF: 0.479

Gnomad SAS AF: 0.507

Gnomad FIN AF: 0.463

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.437

Gnomad OTH AF: 0.467

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

GnomAD4 genome AF: 0.466 AC: 70772 AN: 151838 Hom.: 16586 Cov.: 31 AF XY: 0.467 AC XY: 34664 AN XY: 74202

Gnomad4 AFR AF: 0.519

Gnomad4 AMR AF: 0.442

Gnomad4 ASJ AF: 0.429

Gnomad4 EAS AF: 0.480

Gnomad4 SAS AF: 0.507

Gnomad4 FIN AF: 0.463

Gnomad4 NFE AF: 0.437

Gnomad4 OTH AF: 0.464

Alfa AF: 0.443 Hom.: 29088

Bravo AF: 0.466

Asia WGS AF: 0.482 AC: 1676 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.7
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: rs10839752; hg19: chr11-7283249;