chr11-7468588-A-C

Position:

• chr11-7468588-A-C

Variant summary

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

The NM_175733.4(SYT9):​c.*1788A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.583 in 340,782 control chromosomes in the GnomAD database, including 58,956 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 0.60 (27718 hom., cov: 33)
  • Exomes 𝑓: 0.57 (31238 hom.)
• Consequence: SYT9 NM_175733.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.15

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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.641 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SYT9	NM_175733.4	c.*1788A>C		3_prime_UTR_variant	7/7	ENST00000318881.11
SYT9	XM_011519901.3	c.*1720A>C		3_prime_UTR_variant	8/8
SYT9	XM_047426379.1	c.*1788A>C		3_prime_UTR_variant	7/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SYT9	ENST00000318881.11	c.*1788A>C		3_prime_UTR_variant	7/7	1	NM_175733.4	P1
SYT9-AS1	ENST00000530201.2	n.1351-18146T>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.599 AC: 91055 AN: 152004 Hom.: 27673 Cov.: 33

Gnomad AFR AF: 0.647

Gnomad AMI AF: 0.515

Gnomad AMR AF: 0.625

Gnomad ASJ AF: 0.482

Gnomad EAS AF: 0.327

Gnomad SAS AF: 0.569

Gnomad FIN AF: 0.628

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.591

Gnomad OTH AF: 0.580

GnomAD4 exome AF: 0.570 AC: 107541 AN: 188658 Hom.: 31238 Cov.: 0 AF XY: 0.570 AC XY: 54545 AN XY: 95768

Gnomad4 AFR exome AF: 0.639

Gnomad4 AMR exome AF: 0.644

Gnomad4 ASJ exome AF: 0.489

Gnomad4 EAS exome AF: 0.346

Gnomad4 SAS exome AF: 0.574

Gnomad4 FIN exome AF: 0.633

Gnomad4 NFE exome AF: 0.592

Gnomad4 OTH exome AF: 0.567

GnomAD4 genome AF: 0.599 AC: 91161 AN: 152124 Hom.: 27718 Cov.: 33 AF XY: 0.601 AC XY: 44657 AN XY: 74352

Gnomad4 AFR AF: 0.647

Gnomad4 AMR AF: 0.625

Gnomad4 ASJ AF: 0.482

Gnomad4 EAS AF: 0.327

Gnomad4 SAS AF: 0.569

Gnomad4 FIN AF: 0.628

Gnomad4 NFE AF: 0.591

Gnomad4 OTH AF: 0.582

Alfa AF: 0.585 Hom.: 37913

Bravo AF: 0.599

Asia WGS AF: 0.480 AC: 1668 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.7
DANN	Benign	0.65

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: rs4351800; hg19: chr11-7489819;