12-79260538-C-T

Variant names:

• chr12-79260538-C-T
• rs1245840
• NM_005639.3:c.167-25249C>T

Variant summary

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

The NM_005639.3(SYT1):​c.167-25249C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.71 in 152,074 control chromosomes in the GnomAD database, including 38,889 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 0.71 (38889 hom., cov: 31)
• Consequence: SYT1 NM_005639.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.737
• Publications: 4 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 (AFR) allele frequency at 95% confidence interval = 0.788 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.167-25249C>T		intron	N/A	NP_005630.1
	SYT1	NM_001135805.2		c.167-25249C>T		intron	N/A	NP_001129277.1
	SYT1	NM_001135806.2		c.167-25249C>T		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.167-25249C>T		intron	N/A	ENSP00000261205.4
	SYT1	ENST00000393240.7	TSL:1	c.167-25249C>T		intron	N/A	ENSP00000376932.3
	SYT1	ENST00000552744.5	TSL:1	c.167-25249C>T		intron	N/A	ENSP00000447575.1

Frequencies

GnomAD3 genomes AF: 0.710 AC: 107953 AN: 151956 Hom.: 38873 Cov.: 31

Gnomad AFR AF: 0.795

Gnomad AMI AF: 0.860

Gnomad AMR AF: 0.730

Gnomad ASJ AF: 0.620

Gnomad EAS AF: 0.414

Gnomad SAS AF: 0.542

Gnomad FIN AF: 0.728

Gnomad MID AF: 0.636

Gnomad NFE AF: 0.690

Gnomad OTH AF: 0.692

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

GnomAD4 genome AF: 0.710 AC: 108004 AN: 152074 Hom.: 38889 Cov.: 31 AF XY: 0.706 AC XY: 52518 AN XY: 74346

African (AFR) AF: 0.795 AC: 32971 AN: 41484

American (AMR) AF: 0.730 AC: 11145 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.620 AC: 2150 AN: 3466

East Asian (EAS) AF: 0.414 AC: 2137 AN: 5164

South Asian (SAS) AF: 0.541 AC: 2609 AN: 4824

European-Finnish (FIN) AF: 0.728 AC: 7713 AN: 10590

Middle Eastern (MID) AF: 0.633 AC: 186 AN: 294

European-Non Finnish (NFE) AF: 0.690 AC: 46869 AN: 67964

Other (OTH) AF: 0.683 AC: 1440 AN: 2108

Alfa AF: 0.683 Hom.: 25741

Bravo AF: 0.718

Asia WGS AF: 0.480 AC: 1671 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	2.2
DANN	Benign	0.43
PhyloP100		0.74
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: rs1245840; hg19: chr12-79654318;