rs4757993

chr11-7417862-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.1166-95G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.551 in 1,330,030 control chromosomes in the GnomAD database, including 209,815 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 0.49 (19325 hom., cov: 31)
  • Exomes 𝑓: 0.56 (190490 hom.)
• Consequence: SYT9 NM_175733.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.232

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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.59 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SYT9	NM_175733.4	c.1166-95G>T		intron_variant		ENST00000318881.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SYT9	ENST00000318881.11	c.1166-95G>T		intron_variant		1	NM_175733.4	P1
SYT9	ENST00000524820.6	c.*263-95G>T		intron_variant, NMD_transcript_variant		2
SYT9	ENST00000532592.1	c.*97-95G>T		intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.485 AC: 73738 AN: 151882 Hom.: 19321 Cov.: 31

Gnomad AFR AF: 0.318

Gnomad AMI AF: 0.632

Gnomad AMR AF: 0.466

Gnomad ASJ AF: 0.708

Gnomad EAS AF: 0.187

Gnomad SAS AF: 0.430

Gnomad FIN AF: 0.539

Gnomad MID AF: 0.611

Gnomad NFE AF: 0.595

Gnomad OTH AF: 0.537

GnomAD4 exome AF: 0.560 AC: 659314 AN: 1178030 Hom.: 190490 AF XY: 0.559 AC XY: 327244 AN XY: 585658

Gnomad4 AFR exome AF: 0.310

Gnomad4 AMR exome AF: 0.366

Gnomad4 ASJ exome AF: 0.711

Gnomad4 EAS exome AF: 0.197

Gnomad4 SAS exome AF: 0.449

Gnomad4 FIN exome AF: 0.529

Gnomad4 NFE exome AF: 0.595

Gnomad4 OTH exome AF: 0.541

GnomAD4 genome AF: 0.485 AC: 73772 AN: 152000 Hom.: 19325 Cov.: 31 AF XY: 0.480 AC XY: 35641 AN XY: 74296

Gnomad4 AFR AF: 0.319

Gnomad4 AMR AF: 0.465

Gnomad4 ASJ AF: 0.708

Gnomad4 EAS AF: 0.187

Gnomad4 SAS AF: 0.431

Gnomad4 FIN AF: 0.539

Gnomad4 NFE AF: 0.594

Gnomad4 OTH AF: 0.530

Alfa AF: 0.577 Hom.: 33226

Bravo AF: 0.467

Asia WGS AF: 0.286 AC: 997 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	0.074
Dann	Benign	0.46

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs4757993; hg19: chr11-7439093;