12-79059913-C-T

Variant names:

• chr12-79059913-C-T
• rs12317960
• NM_005639.3:c.-18+12551C>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.-18+12551C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.174 in 152,080 control chromosomes in the GnomAD database, including 2,367 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 0.17 (2367 hom., cov: 32)
• Consequence: SYT1 NM_005639.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.15
• 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)

LOC105369863 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.23 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYT1	NM_005639.3	c.-18+12551C>T		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.-18+12551C>T		intron_variant	Intron 3 of 10	1	NM_005639.3	ENSP00000261205.4

Frequencies

GnomAD3 genomes AF: 0.174 AC: 26395 AN: 151964 Hom.: 2346 Cov.: 32

Gnomad AFR AF: 0.233

Gnomad AMI AF: 0.0384

Gnomad AMR AF: 0.164

Gnomad ASJ AF: 0.174

Gnomad EAS AF: 0.238

Gnomad SAS AF: 0.237

Gnomad FIN AF: 0.122

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.141

Gnomad OTH AF: 0.164

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

GnomAD4 genome AF: 0.174 AC: 26462 AN: 152080 Hom.: 2367 Cov.: 32 AF XY: 0.174 AC XY: 12960 AN XY: 74356

African (AFR) AF: 0.234 AC: 9700 AN: 41470

American (AMR) AF: 0.164 AC: 2503 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.174 AC: 602 AN: 3468

East Asian (EAS) AF: 0.238 AC: 1229 AN: 5164

South Asian (SAS) AF: 0.237 AC: 1143 AN: 4816

European-Finnish (FIN) AF: 0.122 AC: 1297 AN: 10606

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.141 AC: 9563 AN: 67984

Other (OTH) AF: 0.167 AC: 352 AN: 2106

Alfa AF: 0.167 Hom.: 311

Bravo AF: 0.180

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.29
DANN	Benign	0.38
PhyloP100		-2.2
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: rs12317960; hg19: chr12-79453693;