rs16924131

Positions:

• chr11-7267474-T-C
• chr11-7267474-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_175733.4(SYT9):​c.145+15143T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0229 in 151,664 control chromosomes in the GnomAD database, including 48 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 0.023 (48 hom., cov: 32)
• Consequence: SYT9 NM_175733.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.459

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=-0.96).
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0229 (3471/151664) while in subpopulation AFR AF= 0.0406 (1682/41416). AF 95% confidence interval is 0.039. There are 48 homozygotes in gnomad4. There are 1648 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 48 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SYT9	NM_175733.4	c.145+15143T>C		intron_variant		ENST00000318881.11	NP_783860.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SYT9	ENST00000318881.11	c.145+15143T>C		intron_variant		1	NM_175733.4	ENSP00000324419.6
SYT9	ENST00000524820.6	n.49+28558T>C		intron_variant		2		ENSP00000432141.2
SYT9	ENST00000532592.1	n.145+15143T>C		intron_variant		2		ENSP00000434558.1

Frequencies

GnomAD3 genomes AF: 0.0229 AC: 3468 AN: 151546 Hom.: 48 Cov.: 32

Gnomad AFR AF: 0.0406

Gnomad AMI AF: 0.00768

Gnomad AMR AF: 0.0140

Gnomad ASJ AF: 0.0381

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.0173

Gnomad FIN AF: 0.0122

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0171

Gnomad OTH AF: 0.0259

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

GnomAD4 genome AF: 0.0229 AC: 3471 AN: 151664 Hom.: 48 Cov.: 32 AF XY: 0.0222 AC XY: 1648 AN XY: 74076

Gnomad4 AFR AF: 0.0406

Gnomad4 AMR AF: 0.0140

Gnomad4 ASJ AF: 0.0381

Gnomad4 EAS AF: 0.000580

Gnomad4 SAS AF: 0.0166

Gnomad4 FIN AF: 0.0122

Gnomad4 NFE AF: 0.0171

Gnomad4 OTH AF: 0.0257

Alfa AF: 0.00207 Hom.: 1

Bravo AF: 0.0243

Asia WGS AF: 0.00551 AC: 19 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.92
DANN	Benign	0.53

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: rs16924131; hg19: chr11-7288705;