rs10735416

Variant names:

• chr12-79191123-T-C
• rs10735416
• NM_005639.3:c.-17-26380T>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.-17-26380T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.705 in 150,890 control chromosomes in the GnomAD database, including 37,978 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 (37978 hom., cov: 31)
• Consequence: SYT1 NM_005639.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.807
• 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)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.767 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYT1	NM_005639.3	c.-17-26380T>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.-17-26380T>C		intron_variant	Intron 3 of 10	1	NM_005639.3	ENSP00000261205.4

Frequencies

GnomAD3 genomes AF: 0.705 AC: 106315 AN: 150774 Hom.: 37943 Cov.: 31

Gnomad AFR AF: 0.774

Gnomad AMI AF: 0.859

Gnomad AMR AF: 0.730

Gnomad ASJ AF: 0.644

Gnomad EAS AF: 0.424

Gnomad SAS AF: 0.515

Gnomad FIN AF: 0.733

Gnomad MID AF: 0.669

Gnomad NFE AF: 0.690

Gnomad OTH AF: 0.697

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

GnomAD4 genome AF: 0.705 AC: 106385 AN: 150890 Hom.: 37978 Cov.: 31 AF XY: 0.701 AC XY: 51700 AN XY: 73712

African (AFR) AF: 0.774 AC: 31881 AN: 41206

American (AMR) AF: 0.730 AC: 11069 AN: 15160

Ashkenazi Jewish (ASJ) AF: 0.644 AC: 2228 AN: 3460

East Asian (EAS) AF: 0.424 AC: 2181 AN: 5146

South Asian (SAS) AF: 0.513 AC: 2473 AN: 4820

European-Finnish (FIN) AF: 0.733 AC: 7447 AN: 10164

Middle Eastern (MID) AF: 0.670 AC: 193 AN: 288

European-Non Finnish (NFE) AF: 0.690 AC: 46685 AN: 67638

Other (OTH) AF: 0.690 AC: 1448 AN: 2100

Alfa AF: 0.689 Hom.: 19435

Bravo AF: 0.713

Asia WGS AF: 0.477 AC: 1646 AN: 3446

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	7.3
DANN	Benign	0.64
PhyloP100		0.81
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: rs10735416; hg19: chr12-79584903;