rs1245804

Variant names:

• chr12-79241891-G-A
• rs1245804
• NM_005639.3:c.166+24206G>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.166+24206G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.688 in 151,954 control chromosomes in the GnomAD database, including 36,277 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 0.69 (36277 hom., cov: 31)
• Consequence: SYT1 NM_005639.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.20
• 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)

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 (AMR) allele frequency at 95% confidence interval = 0.709 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYT1	NM_005639.3	c.166+24206G>A		intron_variant	Intron 4 of 10	ENST00000261205.9	NP_005630.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYT1	ENST00000261205.9	c.166+24206G>A		intron_variant	Intron 4 of 10	1	NM_005639.3	ENSP00000261205.4

Frequencies

GnomAD3 genomes AF: 0.688 AC: 104431 AN: 151836 Hom.: 36262 Cov.: 31

Gnomad AFR AF: 0.713

Gnomad AMI AF: 0.859

Gnomad AMR AF: 0.720

Gnomad ASJ AF: 0.625

Gnomad EAS AF: 0.432

Gnomad SAS AF: 0.521

Gnomad FIN AF: 0.737

Gnomad MID AF: 0.636

Gnomad NFE AF: 0.690

Gnomad OTH AF: 0.677

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

GnomAD4 genome AF: 0.688 AC: 104476 AN: 151954 Hom.: 36277 Cov.: 31 AF XY: 0.685 AC XY: 50858 AN XY: 74264

African (AFR) AF: 0.713 AC: 29532 AN: 41428

American (AMR) AF: 0.720 AC: 11007 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.625 AC: 2168 AN: 3470

East Asian (EAS) AF: 0.432 AC: 2216 AN: 5128

South Asian (SAS) AF: 0.520 AC: 2496 AN: 4804

European-Finnish (FIN) AF: 0.737 AC: 7786 AN: 10570

Middle Eastern (MID) AF: 0.633 AC: 186 AN: 294

European-Non Finnish (NFE) AF: 0.690 AC: 46890 AN: 67952

Other (OTH) AF: 0.668 AC: 1413 AN: 2114

Alfa AF: 0.688 Hom.: 99993

Bravo AF: 0.692

Asia WGS AF: 0.481 AC: 1675 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	0.34
DANN	Benign	0.75
PhyloP100		-1.2
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: rs1245804; hg19: chr12-79635671;