rs12312807

Variant names:

• chr12-79039425-G-A
• rs12312807
• NM_005639.3:c.-83-7872G>A

Variant summary

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

The NM_005639.3(SYT1):​c.-83-7872G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.108 in 151,838 control chromosomes in the GnomAD database, including 924 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 0.11 (924 hom., cov: 31)
• Consequence: SYT1 NM_005639.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.121
• 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)

ENSG00000257191 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.222 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYT1	NM_005639.3	c.-83-7872G>A		intron_variant	Intron 2 of 10	ENST00000261205.9	NP_005630.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYT1	ENST00000261205.9	c.-83-7872G>A		intron_variant	Intron 2 of 10	1	NM_005639.3	ENSP00000261205.4

Frequencies

GnomAD3 genomes AF: 0.108 AC: 16424 AN: 151722 Hom.: 918 Cov.: 31

Gnomad AFR AF: 0.0745

Gnomad AMI AF: 0.0384

Gnomad AMR AF: 0.129

Gnomad ASJ AF: 0.134

Gnomad EAS AF: 0.233

Gnomad SAS AF: 0.200

Gnomad FIN AF: 0.0939

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.110

Gnomad OTH AF: 0.107

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

GnomAD4 genome AF: 0.108 AC: 16449 AN: 151838 Hom.: 924 Cov.: 31 AF XY: 0.111 AC XY: 8214 AN XY: 74216

African (AFR) AF: 0.0748 AC: 3103 AN: 41468

American (AMR) AF: 0.128 AC: 1955 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.134 AC: 464 AN: 3454

East Asian (EAS) AF: 0.233 AC: 1195 AN: 5134

South Asian (SAS) AF: 0.199 AC: 959 AN: 4808

European-Finnish (FIN) AF: 0.0939 AC: 991 AN: 10550

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.110 AC: 7500 AN: 67878

Other (OTH) AF: 0.112 AC: 235 AN: 2106

Alfa AF: 0.111 Hom.: 205

Bravo AF: 0.110

Asia WGS AF: 0.180 AC: 626 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.4
DANN	Benign	0.42
PhyloP100		-0.12
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: rs12312807; hg19: chr12-79433205;