11-7262018-G-T

Variant names:

• chr11-7262018-G-T
• rs10839752
• NM_175733.4:c.145+9687G>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.514 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_175733.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYT9	NM_175733.4	MANE Select	c.145+9687G>T		intron	N/A	NP_783860.1	Q86SS6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYT9	ENST00000318881.11	TSL:1 MANE Select	c.145+9687G>T		intron	N/A	ENSP00000324419.6	Q86SS6
	SYT9	ENST00000524820.6	TSL:2	n.49+23102G>T		intron	N/A	ENSP00000432141.2	E9PDN4
	SYT9	ENST00000532592.1	TSL:2	n.145+9687G>T		intron	N/A	ENSP00000434558.1	B3KNT7

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

African (AFR) AF: 0.519 AC: 21489 AN: 41378

American (AMR) AF: 0.442 AC: 6746 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.429 AC: 1488 AN: 3472

East Asian (EAS) AF: 0.480 AC: 2462 AN: 5130

South Asian (SAS) AF: 0.507 AC: 2445 AN: 4822

European-Finnish (FIN) AF: 0.463 AC: 4881 AN: 10542

Middle Eastern (MID) AF: 0.459 AC: 134 AN: 292

European-Non Finnish (NFE) AF: 0.437 AC: 29693 AN: 67916

Other (OTH) AF: 0.464 AC: 977 AN: 2104

Alfa AF: 0.448 Hom.: 40405

Bravo AF: 0.466

Asia WGS AF: 0.482 AC: 1676 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.7
DANN	Benign	0.72
PhyloP100		0.32
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: rs10839752; hg19: chr11-7283249;