rs907609

chr11-1836040-C-T

Variant summary

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

The NM_001394072.1(SYT8):c.357+56C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.154 in 1,584,954 control chromosomes in the GnomAD database, including 19,706 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 0.14 (1715 hom., cov: 34)
  • Exomes 𝑓: 0.16 (17991 hom.)
• Consequence: SYT8 NM_001394072.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.66

Genes affected

SYT8 (HGNC:19264): (synaptotagmin 8) This gene encodes a member of the synaptotagmin protein family. Synaptotagmins are membrane proteins that are important in neurotransmission and hormone secretion, both of which involve regulated exocytosis. Expression of the encoded protein in human pancreatic islets has been connected to activity of the promoter for the insulin gene, on the same chromosome several hundred kilobases away (PMID: 21336277 and 22928559). This association would link response to gluclose to insulin secretion. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Mar 2014]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.184 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SYT8	NM_001394072.1	c.357+56C>T		intron_variant		ENST00000341958.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SYT8	ENST00000341958.4	c.357+56C>T		intron_variant		5	NM_001394072.1	P2

Frequencies

GnomAD3 genomes AF: 0.144 AC: 21911 AN: 152062 Hom.: 1708 Cov.: 34

Gnomad AFR AF: 0.0954

Gnomad AMI AF: 0.128

Gnomad AMR AF: 0.189

Gnomad ASJ AF: 0.144

Gnomad EAS AF: 0.0725

Gnomad SAS AF: 0.182

Gnomad FIN AF: 0.233

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.153

Gnomad OTH AF: 0.148

GnomAD3 exomes AF: 0.166 AC: 37238 AN: 224428 Hom.: 3250 AF XY: 0.165 AC XY: 20325 AN XY: 123138

Gnomad AFR exome AF: 0.0979

Gnomad AMR exome AF: 0.224

Gnomad ASJ exome AF: 0.146

Gnomad EAS exome AF: 0.0687

Gnomad SAS exome AF: 0.187

Gnomad FIN exome AF: 0.239

Gnomad NFE exome AF: 0.156

Gnomad OTH exome AF: 0.184

GnomAD4 exome AF: 0.155 AC: 222164 AN: 1432774 Hom.: 17991 Cov.: 34 AF XY: 0.156 AC XY: 110687 AN XY: 711474

Gnomad4 AFR exome AF: 0.0966

Gnomad4 AMR exome AF: 0.215

Gnomad4 ASJ exome AF: 0.143

Gnomad4 EAS exome AF: 0.0736

Gnomad4 SAS exome AF: 0.184

Gnomad4 FIN exome AF: 0.237

Gnomad4 NFE exome AF: 0.152

Gnomad4 OTH exome AF: 0.154

GnomAD4 genome AF: 0.144 AC: 21940 AN: 152180 Hom.: 1715 Cov.: 34 AF XY: 0.147 AC XY: 10932 AN XY: 74388

Gnomad4 AFR AF: 0.0954

Gnomad4 AMR AF: 0.190

Gnomad4 ASJ AF: 0.144

Gnomad4 EAS AF: 0.0727

Gnomad4 SAS AF: 0.182

Gnomad4 FIN AF: 0.233

Gnomad4 NFE AF: 0.152

Gnomad4 OTH AF: 0.149

Alfa AF: 0.151 Hom.: 3167

Bravo AF: 0.138

Asia WGS AF: 0.153 AC: 531 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.12
Dann	Benign	0.83
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: rs907609; hg19: chr11-1857270; COSMIC: COSV53288531; COSMIC: COSV53288531;