11-7376568-T-C

Position:

• chr11-7376568-T-C

Variant summary

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

The NM_175733.4(SYT9):​c.1045-39474T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.251 in 152,010 control chromosomes in the GnomAD database, including 6,144 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 0.25 (6144 hom., cov: 30)
• Consequence: SYT9 NM_175733.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.478

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=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.606 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SYT9	NM_175733.4	c.1045-39474T>C		intron_variant		ENST00000318881.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SYT9	ENST00000318881.11	c.1045-39474T>C		intron_variant		1	NM_175733.4	P1
SYT9	ENST00000524820.6	c.*142-39474T>C		intron_variant, NMD_transcript_variant		2
SYT9	ENST00000532592.1	c.498-39474T>C		intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.251 AC: 38158 AN: 151892 Hom.: 6141 Cov.: 30

Gnomad AFR AF: 0.0820

Gnomad AMI AF: 0.0921

Gnomad AMR AF: 0.372

Gnomad ASJ AF: 0.347

Gnomad EAS AF: 0.625

Gnomad SAS AF: 0.457

Gnomad FIN AF: 0.318

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.269

Gnomad OTH AF: 0.293

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

GnomAD4 genome AF: 0.251 AC: 38179 AN: 152010 Hom.: 6144 Cov.: 30 AF XY: 0.263 AC XY: 19563 AN XY: 74278

Gnomad4 AFR AF: 0.0820

Gnomad4 AMR AF: 0.372

Gnomad4 ASJ AF: 0.347

Gnomad4 EAS AF: 0.624

Gnomad4 SAS AF: 0.457

Gnomad4 FIN AF: 0.318

Gnomad4 NFE AF: 0.269

Gnomad4 OTH AF: 0.300

Alfa AF: 0.278 Hom.: 6039

Bravo AF: 0.247

Asia WGS AF: 0.503 AC: 1746 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	9.6
DANN	Benign	0.88

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: rs2346824; hg19: chr11-7397799;