rs10506800

Positions:

• chr12-78982937-T-C

Variant summary

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

The ENST00000261205.9(SYT1):​c.-84+5006T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0883 in 152,162 control chromosomes in the GnomAD database, including 762 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 0.088 (762 hom., cov: 32)
• Consequence: SYT1 ENST00000261205.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.88

Genes affected

SYT1 (HGNC:11509): (synaptotagmin 1) This gene encodes a member of the synaptotagmin protein family. The synaptotagmins are integral membrane proteins of synaptic vesicles that serve as calcium sensors in the process of vesicular trafficking and exocytosis. The encoded protein participates in triggering neurotransmitter release at the synapse in response to calcium binding. Mutations in this gene are associated with Baker-Gordon syndrome. [provided by RefSeq, Jan 2023]

(HGNC:):

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 (AFR) allele frequency at 95% confidence interval = 0.151 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SYT1	NM_005639.3	c.-84+5006T>C		intron_variant		ENST00000261205.9	NP_005630.1
LOC105369863	XR_007063385.1	n.30565-6268A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SYT1	ENST00000261205.9	c.-84+5006T>C		intron_variant		1	NM_005639.3	ENSP00000261205	P3
	ENST00000548384.1	n.183-6268A>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0881 AC: 13395 AN: 152044 Hom.: 751 Cov.: 32

Gnomad AFR AF: 0.153

Gnomad AMI AF: 0.0307

Gnomad AMR AF: 0.106

Gnomad ASJ AF: 0.0829

Gnomad EAS AF: 0.00405

Gnomad SAS AF: 0.0555

Gnomad FIN AF: 0.0583

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0596

Gnomad OTH AF: 0.0717

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

GnomAD4 genome AF: 0.0883 AC: 13439 AN: 152162 Hom.: 762 Cov.: 32 AF XY: 0.0876 AC XY: 6516 AN XY: 74390

Gnomad4 AFR AF: 0.154

Gnomad4 AMR AF: 0.106

Gnomad4 ASJ AF: 0.0829

Gnomad4 EAS AF: 0.00387

Gnomad4 SAS AF: 0.0551

Gnomad4 FIN AF: 0.0583

Gnomad4 NFE AF: 0.0596

Gnomad4 OTH AF: 0.0738

Alfa AF: 0.0827 Hom.: 60

Bravo AF: 0.0973

Asia WGS AF: 0.0530 AC: 184 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.090
DANN	Benign	0.45

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: rs10506800; hg19: chr12-79376717;