rs1033196

Positions:

• chr12-79049057-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+1695G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.199 in 151,672 control chromosomes in the GnomAD database, including 3,357 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 0.20 (3357 hom., cov: 32)
• Consequence: SYT1 NM_005639.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.40

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=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.294 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SYT1	NM_005639.3	c.-18+1695G>A		intron_variant		ENST00000261205.9	NP_005630.1
LOC105369863	XR_007063385.1	n.30477-12484C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SYT1	ENST00000261205.9	c.-18+1695G>A		intron_variant		1	NM_005639.3	ENSP00000261205	P3

Frequencies

GnomAD3 genomes AF: 0.199 AC: 30162 AN: 151554 Hom.: 3320 Cov.: 32

Gnomad AFR AF: 0.283

Gnomad AMI AF: 0.0384

Gnomad AMR AF: 0.246

Gnomad ASJ AF: 0.187

Gnomad EAS AF: 0.307

Gnomad SAS AF: 0.240

Gnomad FIN AF: 0.123

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.142

Gnomad OTH AF: 0.190

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

GnomAD4 genome AF: 0.199 AC: 30257 AN: 151672 Hom.: 3357 Cov.: 32 AF XY: 0.202 AC XY: 14951 AN XY: 74112

Gnomad4 AFR AF: 0.284

Gnomad4 AMR AF: 0.247

Gnomad4 ASJ AF: 0.187

Gnomad4 EAS AF: 0.307

Gnomad4 SAS AF: 0.241

Gnomad4 FIN AF: 0.123

Gnomad4 NFE AF: 0.142

Gnomad4 OTH AF: 0.196

Alfa AF: 0.167 Hom.: 1167

Bravo AF: 0.215

Asia WGS AF: 0.265 AC: 922 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.013
DANN	Benign	0.39

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: rs1033196; hg19: chr12-79442837;