rs10500695

Variant names:

• chr11-7354396-T-C
• rs10500695
• NM_175733.4:c.1044+40455T>C

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+40455T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0321 in 152,298 control chromosomes in the GnomAD database, including 183 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 0.032 (183 hom., cov: 32)
• Consequence: SYT9 NM_175733.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.661
• Publications: 1 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0891 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYT9	NM_175733.4	c.1044+40455T>C		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+40455T>C		intron_variant	Intron 3 of 6	1	NM_175733.4	ENSP00000324419.6
SYT9	ENST00000524820.6	n.*141+40059T>C		intron_variant	Intron 4 of 8	2		ENSP00000432141.2
SYT9	ENST00000532592.1	n.497+51006T>C		intron_variant	Intron 2 of 5	2		ENSP00000434558.1

Frequencies

GnomAD3 genomes AF: 0.0320 AC: 4874 AN: 152180 Hom.: 182 Cov.: 32

Gnomad AFR AF: 0.0914

Gnomad AMI AF: 0.0209

Gnomad AMR AF: 0.0162

Gnomad ASJ AF: 0.00634

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00160

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0106

Gnomad OTH AF: 0.0253

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

GnomAD4 genome AF: 0.0321 AC: 4889 AN: 152298 Hom.: 183 Cov.: 32 AF XY: 0.0306 AC XY: 2278 AN XY: 74484

African (AFR) AF: 0.0915 AC: 3801 AN: 41540

American (AMR) AF: 0.0162 AC: 248 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00634 AC: 22 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4826

European-Finnish (FIN) AF: 0.00160 AC: 17 AN: 10626

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.0106 AC: 723 AN: 68032

Other (OTH) AF: 0.0250 AC: 53 AN: 2116

Alfa AF: 0.0268 Hom.: 41

Bravo AF: 0.0360

Asia WGS AF: 0.00866 AC: 30 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	6.7
DANN	Benign	0.72
PhyloP100		0.66
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: rs10500695; hg19: chr11-7375627;