rs907609

Variant names:

• chr11-1836040-C-T
• rs907609
• ENST00000490707.5:n.2249C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000490707.5(SYT8):​n.2249C>T variant causes a non coding transcript exon 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 ENST00000490707.5 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.66
• Publications: 14 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.008).
• 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 rank	MANE	Protein	UniProt
SYT8	NM_001394072.1	c.357+56C>T		intron_variant	Intron 3 of 7	ENST00000341958.4	NP_001381001.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYT8	ENST00000341958.4	c.357+56C>T		intron_variant	Intron 3 of 7	5	NM_001394072.1	ENSP00000343691.3

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

GnomAD2 exomes AF: 0.166 AC: 37238 AN: 224428 AF XY: 0.165

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 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

African (AFR) AF: 0.0966 AC: 3096 AN: 32048

American (AMR) AF: 0.215 AC: 8283 AN: 38544

Ashkenazi Jewish (ASJ) AF: 0.143 AC: 3520 AN: 24616

East Asian (EAS) AF: 0.0736 AC: 2888 AN: 39230

South Asian (SAS) AF: 0.184 AC: 15330 AN: 83404

European-Finnish (FIN) AF: 0.237 AC: 12263 AN: 51710

Middle Eastern (MID) AF: 0.177 AC: 998 AN: 5638

European-Non Finnish (NFE) AF: 0.152 AC: 166712 AN: 1098508

Other (OTH) AF: 0.154 AC: 9074 AN: 59076

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

African (AFR) AF: 0.0954 AC: 3965 AN: 41542

American (AMR) AF: 0.190 AC: 2904 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.144 AC: 499 AN: 3470

East Asian (EAS) AF: 0.0727 AC: 376 AN: 5174

South Asian (SAS) AF: 0.182 AC: 880 AN: 4822

European-Finnish (FIN) AF: 0.233 AC: 2463 AN: 10584

Middle Eastern (MID) AF: 0.190 AC: 56 AN: 294

European-Non Finnish (NFE) AF: 0.152 AC: 10366 AN: 67974

Other (OTH) AF: 0.149 AC: 314 AN: 2112

Alfa AF: 0.147 Hom.: 6225

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
PhyloP100		-3.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs907609; hg19: chr11-1857270; COSMIC: COSV53288531; COSMIC: COSV53288531;