12-79111356-T-C

Position:

• chr12-79111356-T-C

Variant summary

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

The ENST00000261205.9(SYT1):​c.-18+63994T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.159 in 151,898 control chromosomes in the GnomAD database, including 2,075 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 0.16 (2075 hom., cov: 32)
• Consequence: SYT1 ENST00000261205.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00400

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.214 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SYT1	NM_005639.3	c.-18+63994T>C		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+63994T>C		intron_variant		1	NM_005639.3	ENSP00000261205	P3

Frequencies

GnomAD3 genomes AF: 0.158 AC: 24036 AN: 151780 Hom.: 2054 Cov.: 32

Gnomad AFR AF: 0.217

Gnomad AMI AF: 0.135

Gnomad AMR AF: 0.104

Gnomad ASJ AF: 0.198

Gnomad EAS AF: 0.135

Gnomad SAS AF: 0.192

Gnomad FIN AF: 0.163

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.132

Gnomad OTH AF: 0.161

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

GnomAD4 genome AF: 0.159 AC: 24105 AN: 151898 Hom.: 2075 Cov.: 32 AF XY: 0.161 AC XY: 11920 AN XY: 74240

Gnomad4 AFR AF: 0.218

Gnomad4 AMR AF: 0.103

Gnomad4 ASJ AF: 0.198

Gnomad4 EAS AF: 0.135

Gnomad4 SAS AF: 0.192

Gnomad4 FIN AF: 0.163

Gnomad4 NFE AF: 0.132

Gnomad4 OTH AF: 0.167

Alfa AF: 0.148 Hom.: 280

Bravo AF: 0.156

Asia WGS AF: 0.187 AC: 652 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	5.8
DANN	Benign	0.64

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: rs11112829; hg19: chr12-79505136;