rs11114027

Variant names:

• chr12-79381468-G-T
• rs11114027
• NM_005639.3:c.928+27849G>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.928+27849G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.121 in 152,250 control chromosomes in the GnomAD database, including 1,173 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 0.12 (1173 hom., cov: 32)
• Consequence: SYT1 NM_005639.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0230
• Publications: 12 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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.136 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYT1	NM_005639.3	c.928+27849G>T		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.928+27849G>T		intron_variant	Intron 9 of 10	1	NM_005639.3	ENSP00000261205.4

Frequencies

GnomAD3 genomes AF: 0.121 AC: 18395 AN: 152132 Hom.: 1171 Cov.: 32

Gnomad AFR AF: 0.0963

Gnomad AMI AF: 0.110

Gnomad AMR AF: 0.122

Gnomad ASJ AF: 0.196

Gnomad EAS AF: 0.0817

Gnomad SAS AF: 0.111

Gnomad FIN AF: 0.101

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.138

Gnomad OTH AF: 0.146

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

GnomAD4 genome AF: 0.121 AC: 18400 AN: 152250 Hom.: 1173 Cov.: 32 AF XY: 0.119 AC XY: 8867 AN XY: 74454

African (AFR) AF: 0.0960 AC: 3989 AN: 41536

American (AMR) AF: 0.122 AC: 1870 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.196 AC: 679 AN: 3472

East Asian (EAS) AF: 0.0821 AC: 426 AN: 5190

South Asian (SAS) AF: 0.111 AC: 534 AN: 4826

European-Finnish (FIN) AF: 0.101 AC: 1066 AN: 10604

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.138 AC: 9384 AN: 68008

Other (OTH) AF: 0.150 AC: 317 AN: 2112

Alfa AF: 0.137 Hom.: 3990

Bravo AF: 0.123

Asia WGS AF: 0.0770 AC: 270 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.93
DANN	Benign	0.34
PhyloP100		-0.023
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: rs11114027; hg19: chr12-79775248;