rs10506791

Variant names:

• chr12-78881264-G-A
• rs10506791
• NM_005639.3:c.-217+16155G>A

Variant summary

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

The NM_005639.3(SYT1):​c.-217+16155G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0313 in 151,232 control chromosomes in the GnomAD database, including 198 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 0.031 (198 hom., cov: 32)
• Consequence: SYT1 NM_005639.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.421
• Publications: 1 publications found

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]

SYT1 Gene-Disease associations (from GenCC):

• infantile hypotonia-oculomotor anomalies-hyperkinetic movements-developmental delay syndrome

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Illumina, G2P, Labcorp Genetics (formerly Invitae)

ENSG00000257191 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.119 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYT1	NM_005639.3	c.-217+16155G>A		intron_variant	Intron 1 of 10	ENST00000261205.9	NP_005630.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYT1	ENST00000261205.9	c.-217+16155G>A		intron_variant	Intron 1 of 10	1	NM_005639.3	ENSP00000261205.4

Frequencies

GnomAD3 genomes AF: 0.0314 AC: 4740 AN: 151114 Hom.: 199 Cov.: 32

Gnomad AFR AF: 0.00707

Gnomad AMI AF: 0.00987

Gnomad AMR AF: 0.124

Gnomad ASJ AF: 0.0243

Gnomad EAS AF: 0.000782

Gnomad SAS AF: 0.0254

Gnomad FIN AF: 0.0523

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0257

Gnomad OTH AF: 0.0299

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

GnomAD4 genome AF: 0.0313 AC: 4738 AN: 151232 Hom.: 198 Cov.: 32 AF XY: 0.0332 AC XY: 2451 AN XY: 73808

African (AFR) AF: 0.00705 AC: 291 AN: 41294

American (AMR) AF: 0.124 AC: 1874 AN: 15118

Ashkenazi Jewish (ASJ) AF: 0.0243 AC: 84 AN: 3458

East Asian (EAS) AF: 0.000980 AC: 5 AN: 5100

South Asian (SAS) AF: 0.0254 AC: 122 AN: 4806

European-Finnish (FIN) AF: 0.0523 AC: 547 AN: 10466

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.0257 AC: 1739 AN: 67688

Other (OTH) AF: 0.0296 AC: 62 AN: 2096

Alfa AF: 0.0270 Hom.: 57

Bravo AF: 0.0352

Asia WGS AF: 0.0160 AC: 58 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.1
DANN	Benign	0.49
PhyloP100		-0.42
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10506791; hg19: chr12-79275044;