12-79046234-T-G

Variant names:

• chr12-79046234-T-G
• rs1527119
• NM_005639.3:c.-83-1063T>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_005639.3(SYT1):​c.-83-1063T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.139 in 152,176 control chromosomes in the GnomAD database, including 1,509 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 0.14 (1509 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: SYT1 NM_005639.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.46
• 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.4).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.223 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.-83-1063T>G		intron	N/A	NP_005630.1
	SYT1	NM_001135805.2		c.-83-1063T>G		intron	N/A	NP_001129277.1
	SYT1	NM_001135806.2		c.-84+408T>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.-83-1063T>G		intron	N/A	ENSP00000261205.4
	SYT1	ENST00000393240.7	TSL:1	c.-83-1063T>G		intron	N/A	ENSP00000376932.3
	SYT1	ENST00000552744.5	TSL:1	c.-84+408T>G		intron	N/A	ENSP00000447575.1

Frequencies

GnomAD3 genomes AF: 0.138 AC: 21050 AN: 152058 Hom.: 1494 Cov.: 32

Gnomad AFR AF: 0.180

Gnomad AMI AF: 0.0384

Gnomad AMR AF: 0.139

Gnomad ASJ AF: 0.134

Gnomad EAS AF: 0.234

Gnomad SAS AF: 0.198

Gnomad FIN AF: 0.0939

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.111

Gnomad OTH AF: 0.128

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

GnomAD4 genome AF: 0.139 AC: 21108 AN: 152176 Hom.: 1509 Cov.: 32 AF XY: 0.140 AC XY: 10408 AN XY: 74410

African (AFR) AF: 0.181 AC: 7492 AN: 41506

American (AMR) AF: 0.138 AC: 2115 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.134 AC: 465 AN: 3470

East Asian (EAS) AF: 0.234 AC: 1211 AN: 5172

South Asian (SAS) AF: 0.198 AC: 952 AN: 4820

European-Finnish (FIN) AF: 0.0939 AC: 997 AN: 10616

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.111 AC: 7546 AN: 67988

Other (OTH) AF: 0.133 AC: 281 AN: 2116

Alfa AF: 0.132 Hom.: 219

Bravo AF: 0.145

Asia WGS AF: 0.189 AC: 659 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.40
CADD	Benign	17
DANN	Benign	0.61
PhyloP100		1.5
PromoterAI		0.025	Neutral
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: rs1527119; hg19: chr12-79440014;