12-79062007-T-C

Variant names:

• chr12-79062007-T-C
• rs11610381
• NM_005639.3:c.-18+14645T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005639.3(SYT1):​c.-18+14645T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.211 in 152,148 control chromosomes in the GnomAD database, including 3,893 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 0.21 (3893 hom., cov: 32)
• Consequence: SYT1 NM_005639.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0430
• Publications: 2 publications found

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]

SYT1 Gene-Disease associations (from GenCC):

• infantile hypotonia-oculomotor anomalies-hyperkinetic movements-developmental delay syndrome

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Illumina, G2P, Labcorp Genetics (formerly Invitae)

LOC105369863 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.319 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYT1	NM_005639.3	c.-18+14645T>C		intron_variant	Intron 3 of 10	ENST00000261205.9	NP_005630.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYT1	ENST00000261205.9	c.-18+14645T>C		intron_variant	Intron 3 of 10	1	NM_005639.3	ENSP00000261205.4

Frequencies

GnomAD3 genomes AF: 0.211 AC: 32023 AN: 152030 Hom.: 3855 Cov.: 32

Gnomad AFR AF: 0.323

Gnomad AMI AF: 0.0384

Gnomad AMR AF: 0.248

Gnomad ASJ AF: 0.187

Gnomad EAS AF: 0.308

Gnomad SAS AF: 0.242

Gnomad FIN AF: 0.123

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.142

Gnomad OTH AF: 0.197

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

GnomAD4 genome AF: 0.211 AC: 32125 AN: 152148 Hom.: 3893 Cov.: 32 AF XY: 0.213 AC XY: 15832 AN XY: 74396

African (AFR) AF: 0.324 AC: 13445 AN: 41510

American (AMR) AF: 0.249 AC: 3799 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.187 AC: 648 AN: 3472

East Asian (EAS) AF: 0.308 AC: 1596 AN: 5178

South Asian (SAS) AF: 0.242 AC: 1170 AN: 4828

European-Finnish (FIN) AF: 0.123 AC: 1307 AN: 10606

Middle Eastern (MID) AF: 0.139 AC: 41 AN: 294

European-Non Finnish (NFE) AF: 0.142 AC: 9655 AN: 67980

Other (OTH) AF: 0.203 AC: 429 AN: 2112

Alfa AF: 0.195 Hom.: 545

Bravo AF: 0.228

Asia WGS AF: 0.269 AC: 937 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.6
DANN	Benign	0.57
PhyloP100		-0.043
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11610381; hg19: chr12-79455787;