rs1245819

Positions:

• chr12-79248577-G-A
• chr12-79248577-G-C

Variant summary

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

The NM_005639.3(SYT1):​c.166+30892G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.726 in 152,060 control chromosomes in the GnomAD database, including 40,762 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 0.73 (40762 hom., cov: 32)
• Consequence: SYT1 NM_005639.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.123

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.834 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SYT1	NM_005639.3	c.166+30892G>A		intron_variant		ENST00000261205.9	NP_005630.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SYT1	ENST00000261205.9	c.166+30892G>A		intron_variant		1	NM_005639.3	ENSP00000261205	P3

Frequencies

GnomAD3 genomes AF: 0.726 AC: 110276 AN: 151942 Hom.: 40730 Cov.: 32

Gnomad AFR AF: 0.842

Gnomad AMI AF: 0.860

Gnomad AMR AF: 0.739

Gnomad ASJ AF: 0.629

Gnomad EAS AF: 0.416

Gnomad SAS AF: 0.545

Gnomad FIN AF: 0.728

Gnomad MID AF: 0.677

Gnomad NFE AF: 0.692

Gnomad OTH AF: 0.714

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

GnomAD4 genome AF: 0.726 AC: 110349 AN: 152060 Hom.: 40762 Cov.: 32 AF XY: 0.722 AC XY: 53642 AN XY: 74332

Gnomad4 AFR AF: 0.842

Gnomad4 AMR AF: 0.739

Gnomad4 ASJ AF: 0.629

Gnomad4 EAS AF: 0.416

Gnomad4 SAS AF: 0.544

Gnomad4 FIN AF: 0.728

Gnomad4 NFE AF: 0.692

Gnomad4 OTH AF: 0.706

Alfa AF: 0.694 Hom.: 48419

Bravo AF: 0.736

Asia WGS AF: 0.494 AC: 1720 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.5
DANN	Benign	0.77

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: rs1245819; hg19: chr12-79642357; COSMIC: COSV54073369;