12-79046234-T-G

Position:

• chr12-79046234-T-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_005639.3(SYT1):​c.-83-1063T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.139 in 152,176 control chromosomes in the GnomAD database, including 1,509 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 0.14 (1509 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: SYT1 NM_005639.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.46

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.4).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.223 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SYT1	NM_005639.3	c.-83-1063T>G		intron_variant		ENST00000261205.9
LOC105369863	XR_007063385.1	n.30477-9661A>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SYT1	ENST00000261205.9	c.-83-1063T>G		intron_variant		1	NM_005639.3	P3

Frequencies

GnomAD3 genomes AF: 0.138 AC: 21050 AN: 152058 Hom.: 1494 Cov.: 32

Gnomad AFR AF: 0.180

Gnomad AMI AF: 0.0384

Gnomad AMR AF: 0.139

Gnomad ASJ AF: 0.134

Gnomad EAS AF: 0.234

Gnomad SAS AF: 0.198

Gnomad FIN AF: 0.0939

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.111

Gnomad OTH AF: 0.128

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

GnomAD4 genome AF: 0.139 AC: 21108 AN: 152176 Hom.: 1509 Cov.: 32 AF XY: 0.140 AC XY: 10408 AN XY: 74410

Gnomad4 AFR AF: 0.181

Gnomad4 AMR AF: 0.138

Gnomad4 ASJ AF: 0.134

Gnomad4 EAS AF: 0.234

Gnomad4 SAS AF: 0.198

Gnomad4 FIN AF: 0.0939

Gnomad4 NFE AF: 0.111

Gnomad4 OTH AF: 0.133

Alfa AF: 0.130 Hom.: 210

Bravo AF: 0.145

Asia WGS AF: 0.189 AC: 659 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.40
CADD	Benign	17
DANN	Benign	0.61

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: rs1527119; hg19: chr12-79440014;