chr12-79055627-G-A

Position:

• chr12-79055627-G-A

Variant summary

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

The NM_005639.3(SYT1):​c.-18+8265G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.244 in 151,700 control chromosomes in the GnomAD database, including 5,757 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 0.24 (5757 hom., cov: 32)
• Consequence: SYT1 NM_005639.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.495

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]

LOC105369863 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.345 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SYT1	NM_005639.3	c.-18+8265G>A		intron_variant		ENST00000261205.9
LOC105369863	XR_007063385.1	n.30476+13346C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SYT1	ENST00000261205.9	c.-18+8265G>A		intron_variant		1	NM_005639.3	P3

Frequencies

GnomAD3 genomes AF: 0.244 AC: 37061 AN: 151584 Hom.: 5763 Cov.: 32

Gnomad AFR AF: 0.0637

Gnomad AMI AF: 0.509

Gnomad AMR AF: 0.293

Gnomad ASJ AF: 0.194

Gnomad EAS AF: 0.131

Gnomad SAS AF: 0.301

Gnomad FIN AF: 0.230

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.349

Gnomad OTH AF: 0.282

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

GnomAD4 genome AF: 0.244 AC: 37044 AN: 151700 Hom.: 5757 Cov.: 32 AF XY: 0.240 AC XY: 17764 AN XY: 74082

Gnomad4 AFR AF: 0.0635

Gnomad4 AMR AF: 0.293

Gnomad4 ASJ AF: 0.194

Gnomad4 EAS AF: 0.130

Gnomad4 SAS AF: 0.301

Gnomad4 FIN AF: 0.230

Gnomad4 NFE AF: 0.349

Gnomad4 OTH AF: 0.277

Alfa AF: 0.324 Hom.: 8943

Bravo AF: 0.237

Asia WGS AF: 0.210 AC: 730 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.71
DANN	Benign	0.68

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: rs2950383; hg19: chr12-79449407;