chr12-79243615-A-C

Position:

• chr12-79243615-A-C

Variant summary

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

The ENST00000261205.9(SYT1):​c.166+25930A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.701 in 151,974 control chromosomes in the GnomAD database, including 37,792 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 0.70 (37792 hom., cov: 31)
• Consequence: SYT1 ENST00000261205.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.188

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=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.753 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SYT1	NM_005639.3	c.166+25930A>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.166+25930A>C		intron_variant		1	NM_005639.3	ENSP00000261205	P3

Frequencies

GnomAD3 genomes AF: 0.701 AC: 106481 AN: 151856 Hom.: 37775 Cov.: 31

Gnomad AFR AF: 0.761

Gnomad AMI AF: 0.860

Gnomad AMR AF: 0.725

Gnomad ASJ AF: 0.625

Gnomad EAS AF: 0.433

Gnomad SAS AF: 0.521

Gnomad FIN AF: 0.736

Gnomad MID AF: 0.636

Gnomad NFE AF: 0.690

Gnomad OTH AF: 0.686

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

GnomAD4 genome AF: 0.701 AC: 106530 AN: 151974 Hom.: 37792 Cov.: 31 AF XY: 0.697 AC XY: 51776 AN XY: 74264

Gnomad4 AFR AF: 0.760

Gnomad4 AMR AF: 0.725

Gnomad4 ASJ AF: 0.625

Gnomad4 EAS AF: 0.433

Gnomad4 SAS AF: 0.519

Gnomad4 FIN AF: 0.736

Gnomad4 NFE AF: 0.690

Gnomad4 OTH AF: 0.677

Alfa AF: 0.688 Hom.: 21343

Bravo AF: 0.707

Asia WGS AF: 0.484 AC: 1684 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	4.7
DANN	Benign	0.72

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: rs1245810; hg19: chr12-79637395; COSMIC: COSV54073336;