11-7374960-A-T

Variant names:

• chr11-7374960-A-T
• rs10769783
• NM_175733.4:c.1045-41082A>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_175733.4(SYT9):​c.1045-41082A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
• Consequence: SYT9 NM_175733.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.77
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.05).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYT9	NM_175733.4	c.1045-41082A>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.1045-41082A>T		intron_variant	Intron 3 of 6	1	NM_175733.4	ENSP00000324419.6
SYT9	ENST00000524820.6	n.*142-41082A>T		intron_variant	Intron 4 of 8	2		ENSP00000432141.2
SYT9	ENST00000532592.1	n.498-41082A>T		intron_variant	Intron 2 of 5	2		ENSP00000434558.1

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 139

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.19
DANN	Benign	0.19
PhyloP100		-2.8

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: rs10769783; hg19: chr11-7396191;