rs7972593

Positions:

• chr12-79095238-C-T

Variant summary

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

The NM_005639.3(SYT1):​c.-18+47876C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.11 in 151,802 control chromosomes in the GnomAD database, including 988 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 0.11 (988 hom., cov: 32)
• Consequence: SYT1 NM_005639.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.305

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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.12 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SYT1	NM_005639.3	c.-18+47876C>T		intron_variant		ENST00000261205.9	NP_005630.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SYT1	ENST00000261205.9	c.-18+47876C>T		intron_variant		1	NM_005639.3	ENSP00000261205.4

Frequencies

GnomAD3 genomes AF: 0.110 AC: 16705 AN: 151684 Hom.: 985 Cov.: 32

Gnomad AFR AF: 0.122

Gnomad AMI AF: 0.107

Gnomad AMR AF: 0.0836

Gnomad ASJ AF: 0.178

Gnomad EAS AF: 0.0309

Gnomad SAS AF: 0.0818

Gnomad FIN AF: 0.0779

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.118

Gnomad OTH AF: 0.119

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

GnomAD4 genome AF: 0.110 AC: 16731 AN: 151802 Hom.: 988 Cov.: 32 AF XY: 0.107 AC XY: 7963 AN XY: 74212

Gnomad4 AFR AF: 0.123

Gnomad4 AMR AF: 0.0834

Gnomad4 ASJ AF: 0.178

Gnomad4 EAS AF: 0.0310

Gnomad4 SAS AF: 0.0821

Gnomad4 FIN AF: 0.0779

Gnomad4 NFE AF: 0.118

Gnomad4 OTH AF: 0.118

Alfa AF: 0.114 Hom.: 466

Bravo AF: 0.111

Asia WGS AF: 0.0580 AC: 203 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	7.6
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: rs7972593; hg19: chr12-79489018;