12-79267493-A-G

Variant names:

• chr12-79267493-A-G
• rs10861755
• NM_005639.3:c.167-18294A>G

Variant summary

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

The NM_005639.3(SYT1):​c.167-18294A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.305 in 152,048 control chromosomes in the GnomAD database, including 7,495 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 0.31 (7495 hom., cov: 32)
• Consequence: SYT1 NM_005639.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.191
• Publications: 3 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)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.567 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005639.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYT1	NM_005639.3	MANE Select	c.167-18294A>G		intron	N/A	NP_005630.1
	SYT1	NM_001135805.2		c.167-18294A>G		intron	N/A	NP_001129277.1
	SYT1	NM_001135806.2		c.167-18294A>G		intron	N/A	NP_001129278.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYT1	ENST00000261205.9	TSL:1 MANE Select	c.167-18294A>G		intron	N/A	ENSP00000261205.4
	SYT1	ENST00000393240.7	TSL:1	c.167-18294A>G		intron	N/A	ENSP00000376932.3
	SYT1	ENST00000552744.5	TSL:1	c.167-18294A>G		intron	N/A	ENSP00000447575.1

Frequencies

GnomAD3 genomes AF: 0.305 AC: 46335 AN: 151930 Hom.: 7468 Cov.: 32

Gnomad AFR AF: 0.258

Gnomad AMI AF: 0.140

Gnomad AMR AF: 0.276

Gnomad ASJ AF: 0.389

Gnomad EAS AF: 0.585

Gnomad SAS AF: 0.458

Gnomad FIN AF: 0.271

Gnomad MID AF: 0.369

Gnomad NFE AF: 0.311

Gnomad OTH AF: 0.320

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

GnomAD4 genome AF: 0.305 AC: 46408 AN: 152048 Hom.: 7495 Cov.: 32 AF XY: 0.309 AC XY: 22946 AN XY: 74326

African (AFR) AF: 0.258 AC: 10707 AN: 41486

American (AMR) AF: 0.276 AC: 4211 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.389 AC: 1349 AN: 3470

East Asian (EAS) AF: 0.585 AC: 3017 AN: 5160

South Asian (SAS) AF: 0.459 AC: 2211 AN: 4818

European-Finnish (FIN) AF: 0.271 AC: 2862 AN: 10556

Middle Eastern (MID) AF: 0.373 AC: 109 AN: 292

European-Non Finnish (NFE) AF: 0.311 AC: 21121 AN: 67970

Other (OTH) AF: 0.328 AC: 693 AN: 2110

Alfa AF: 0.310 Hom.: 12579

Bravo AF: 0.300

Asia WGS AF: 0.523 AC: 1818 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.9
DANN	Benign	0.60
PhyloP100		0.19
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: rs10861755; hg19: chr12-79661273;