11-7464480-C-T

Variant names:

• chr11-7464480-C-T
• rs4628658
• NM_175733.4:c.1468-2312C>T

Variant summary

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

The NM_175733.4(SYT9):​c.1468-2312C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.57 in 151,994 control chromosomes in the GnomAD database, including 24,918 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 0.57 (24918 hom., cov: 32)
• Consequence: SYT9 NM_175733.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.507

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]

SYT9-AS1 (HGNC:56173): (SYT9 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.622 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYT9	NM_175733.4	c.1468-2312C>T		intron_variant	Intron 6 of 6	ENST00000318881.11	NP_783860.1
SYT9	XM_011519901.3	c.1619-2312C>T		intron_variant	Intron 7 of 7		XP_011518203.1
SYT9	XM_047426379.1	c.1372-2312C>T		intron_variant	Intron 6 of 6		XP_047282335.1
SYT9-AS1	NR_103855.1	n.83+1273G>A		intron_variant	Intron 1 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYT9	ENST00000318881.11	c.1468-2312C>T		intron_variant	Intron 6 of 6	1	NM_175733.4	ENSP00000324419.6

Frequencies

GnomAD3 genomes AF: 0.570 AC: 86620 AN: 151876 Hom.: 24912 Cov.: 32

Gnomad AFR AF: 0.629

Gnomad AMI AF: 0.529

Gnomad AMR AF: 0.565

Gnomad ASJ AF: 0.656

Gnomad EAS AF: 0.632

Gnomad SAS AF: 0.521

Gnomad FIN AF: 0.482

Gnomad MID AF: 0.646

Gnomad NFE AF: 0.544

Gnomad OTH AF: 0.569

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

GnomAD4 genome AF: 0.570 AC: 86667 AN: 151994 Hom.: 24918 Cov.: 32 AF XY: 0.565 AC XY: 41975 AN XY: 74282

Gnomad4 AFR AF: 0.629

Gnomad4 AMR AF: 0.564

Gnomad4 ASJ AF: 0.656

Gnomad4 EAS AF: 0.631

Gnomad4 SAS AF: 0.520

Gnomad4 FIN AF: 0.482

Gnomad4 NFE AF: 0.544

Gnomad4 OTH AF: 0.566

Alfa AF: 0.553 Hom.: 31787

Bravo AF: 0.580

Asia WGS AF: 0.550 AC: 1912 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	6.8
DANN	Benign	0.36

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: rs4628658; hg19: chr11-7485711;