rs1356022

Variant names:

• chr12-79056622-A-G
• rs1356022
• NM_005639.3:c.-18+9260A>G

Variant summary

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

The NM_005639.3(SYT1):​c.-18+9260A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.2 in 151,982 control chromosomes in the GnomAD database, including 3,406 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 0.20 (3406 hom., cov: 32)
• Consequence: SYT1 NM_005639.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.123
• Publications: 2 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)

LOC105369863 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.291 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYT1	NM_005639.3	c.-18+9260A>G		intron_variant	Intron 3 of 10	ENST00000261205.9	NP_005630.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYT1	ENST00000261205.9	c.-18+9260A>G		intron_variant	Intron 3 of 10	1	NM_005639.3	ENSP00000261205.4

Frequencies

GnomAD3 genomes AF: 0.200 AC: 30359 AN: 151864 Hom.: 3369 Cov.: 32

Gnomad AFR AF: 0.287

Gnomad AMI AF: 0.0384

Gnomad AMR AF: 0.246

Gnomad ASJ AF: 0.187

Gnomad EAS AF: 0.304

Gnomad SAS AF: 0.242

Gnomad FIN AF: 0.123

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.141

Gnomad OTH AF: 0.189

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

GnomAD4 genome AF: 0.200 AC: 30454 AN: 151982 Hom.: 3406 Cov.: 32 AF XY: 0.202 AC XY: 15042 AN XY: 74306

African (AFR) AF: 0.288 AC: 11924 AN: 41470

American (AMR) AF: 0.247 AC: 3758 AN: 15220

Ashkenazi Jewish (ASJ) AF: 0.187 AC: 647 AN: 3466

East Asian (EAS) AF: 0.304 AC: 1564 AN: 5146

South Asian (SAS) AF: 0.242 AC: 1168 AN: 4822

European-Finnish (FIN) AF: 0.123 AC: 1302 AN: 10602

Middle Eastern (MID) AF: 0.136 AC: 40 AN: 294

European-Non Finnish (NFE) AF: 0.141 AC: 9605 AN: 67940

Other (OTH) AF: 0.195 AC: 411 AN: 2110

Alfa AF: 0.188 Hom.: 495

Bravo AF: 0.216

Asia WGS AF: 0.266 AC: 928 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.3
DANN	Benign	0.82
PhyloP100		-0.12
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: rs1356022; hg19: chr12-79450402;