rs1245665

Variant names:

• chr12-79420283-T-C
• rs1245665
• NM_005639.3:c.929-23790T>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.929-23790T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.878 in 152,130 control chromosomes in the GnomAD database, including 60,881 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 0.88 (60881 hom., cov: 33)
• Consequence: SYT1 NM_005639.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.165
• Publications: 1 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)

ENSG00000257894 (HGNC:58105):

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 (EAS) allele frequency at 95% confidence interval = 0.981 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYT1	NM_005639.3	c.929-23790T>C		intron_variant	Intron 9 of 10	ENST00000261205.9	NP_005630.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYT1	ENST00000261205.9	c.929-23790T>C		intron_variant	Intron 9 of 10	1	NM_005639.3	ENSP00000261205.4

Frequencies

GnomAD3 genomes AF: 0.878 AC: 133535 AN: 152012 Hom.: 60846 Cov.: 33

Gnomad AFR AF: 0.604

Gnomad AMI AF: 0.927

Gnomad AMR AF: 0.949

Gnomad ASJ AF: 0.969

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.989

Gnomad FIN AF: 0.997

Gnomad MID AF: 0.953

Gnomad NFE AF: 0.987

Gnomad OTH AF: 0.912

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

GnomAD4 genome AF: 0.878 AC: 133619 AN: 152130 Hom.: 60881 Cov.: 33 AF XY: 0.884 AC XY: 65730 AN XY: 74372

African (AFR) AF: 0.605 AC: 25065 AN: 41454

American (AMR) AF: 0.949 AC: 14487 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.969 AC: 3366 AN: 3472

East Asian (EAS) AF: 0.999 AC: 5159 AN: 5162

South Asian (SAS) AF: 0.989 AC: 4776 AN: 4828

European-Finnish (FIN) AF: 0.997 AC: 10601 AN: 10628

Middle Eastern (MID) AF: 0.949 AC: 279 AN: 294

European-Non Finnish (NFE) AF: 0.987 AC: 67112 AN: 68006

Other (OTH) AF: 0.913 AC: 1929 AN: 2112

Alfa AF: 0.949 Hom.: 84511

Bravo AF: 0.862

Asia WGS AF: 0.971 AC: 3375 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.3
DANN	Benign	0.78
PhyloP100		-0.17
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: rs1245665; hg19: chr12-79814063;