rs11041321

Variant names:

• chr11-7332638-C-T
• rs11041321
• NM_175733.4:c.1044+18697C>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.1044+18697C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.103 in 152,192 control chromosomes in the GnomAD database, including 960 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 0.10 (960 hom., cov: 33)
• Consequence: SYT9 NM_175733.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.228
• Publications: 3 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=-0.73).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.252 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYT9	NM_175733.4	c.1044+18697C>T		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+18697C>T		intron_variant	Intron 3 of 6	1	NM_175733.4	ENSP00000324419.6
SYT9	ENST00000524820.6	n.*141+18301C>T		intron_variant	Intron 4 of 8	2		ENSP00000432141.2
SYT9	ENST00000532592.1	n.497+29248C>T		intron_variant	Intron 2 of 5	2		ENSP00000434558.1

Frequencies

GnomAD3 genomes AF: 0.103 AC: 15647 AN: 152074 Hom.: 958 Cov.: 33

Gnomad AFR AF: 0.0614

Gnomad AMI AF: 0.110

Gnomad AMR AF: 0.0742

Gnomad ASJ AF: 0.0975

Gnomad EAS AF: 0.263

Gnomad SAS AF: 0.157

Gnomad FIN AF: 0.139

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.114

Gnomad OTH AF: 0.0884

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

GnomAD4 genome AF: 0.103 AC: 15654 AN: 152192 Hom.: 960 Cov.: 33 AF XY: 0.104 AC XY: 7723 AN XY: 74398

African (AFR) AF: 0.0614 AC: 2551 AN: 41554

American (AMR) AF: 0.0740 AC: 1132 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0975 AC: 338 AN: 3468

East Asian (EAS) AF: 0.264 AC: 1361 AN: 5162

South Asian (SAS) AF: 0.157 AC: 759 AN: 4824

European-Finnish (FIN) AF: 0.139 AC: 1474 AN: 10590

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.114 AC: 7721 AN: 67980

Other (OTH) AF: 0.0885 AC: 187 AN: 2114

Alfa AF: 0.104 Hom.: 115

Bravo AF: 0.0952

Asia WGS AF: 0.178 AC: 617 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	12
DANN	Benign	0.69
PhyloP100		0.23
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: rs11041321; hg19: chr11-7353869;