rs1268463

Variant names:

• chr12-79249714-T-G
• rs1268463
• NM_005639.3:c.166+32029T>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.166+32029T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.71 in 152,104 control chromosomes in the GnomAD database, including 38,900 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 0.71 (38900 hom., cov: 31)
• Consequence: SYT1 NM_005639.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.168
• Publications: 3 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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.787 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYT1	NM_005639.3	c.166+32029T>G		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+32029T>G		intron_variant	Intron 4 of 10	1	NM_005639.3	ENSP00000261205.4

Frequencies

GnomAD3 genomes AF: 0.710 AC: 107984 AN: 151986 Hom.: 38883 Cov.: 31

Gnomad AFR AF: 0.795

Gnomad AMI AF: 0.860

Gnomad AMR AF: 0.730

Gnomad ASJ AF: 0.621

Gnomad EAS AF: 0.416

Gnomad SAS AF: 0.543

Gnomad FIN AF: 0.728

Gnomad MID AF: 0.636

Gnomad NFE AF: 0.690

Gnomad OTH AF: 0.693

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

GnomAD4 genome AF: 0.710 AC: 108039 AN: 152104 Hom.: 38900 Cov.: 31 AF XY: 0.706 AC XY: 52522 AN XY: 74348

African (AFR) AF: 0.794 AC: 32959 AN: 41492

American (AMR) AF: 0.730 AC: 11174 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.621 AC: 2154 AN: 3470

East Asian (EAS) AF: 0.416 AC: 2142 AN: 5152

South Asian (SAS) AF: 0.542 AC: 2606 AN: 4810

European-Finnish (FIN) AF: 0.728 AC: 7711 AN: 10588

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

European-Non Finnish (NFE) AF: 0.690 AC: 46882 AN: 67982

Other (OTH) AF: 0.685 AC: 1441 AN: 2104

Alfa AF: 0.694 Hom.: 60607

Bravo AF: 0.718

Asia WGS AF: 0.488 AC: 1698 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.4
DANN	Benign	0.58
PhyloP100		-0.17
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: rs1268463; hg19: chr12-79643494;