12-79111356-T-C

Variant names:

• chr12-79111356-T-C
• rs11112829
• NM_005639.3:c.-18+63994T>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.-18+63994T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.159 in 151,898 control chromosomes in the GnomAD database, including 2,075 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 0.16 (2075 hom., cov: 32)
• Consequence: SYT1 NM_005639.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00400
• Publications: 4 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: Labcorp Genetics (formerly Invitae), Illumina, PanelApp Australia, Ambry Genetics, G2P

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.214 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYT1	NM_005639.3	MANE Select	c.-18+63994T>C		intron	N/A	NP_005630.1	P21579
	SYT1	NM_001135805.2		c.-18+63994T>C		intron	N/A	NP_001129277.1	P21579
	SYT1	NM_001135806.2		c.-18+63994T>C		intron	N/A	NP_001129278.1	P21579

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYT1	ENST00000261205.9	TSL:1 MANE Select	c.-18+63994T>C		intron	N/A	ENSP00000261205.4	P21579
	SYT1	ENST00000393240.7	TSL:1	c.-18+63994T>C		intron	N/A	ENSP00000376932.3	P21579
	SYT1	ENST00000552744.5	TSL:1	c.-18+63994T>C		intron	N/A	ENSP00000447575.1	P21579

Frequencies

GnomAD3 genomes AF: 0.158 AC: 24036 AN: 151780 Hom.: 2054 Cov.: 32

Gnomad AFR AF: 0.217

Gnomad AMI AF: 0.135

Gnomad AMR AF: 0.104

Gnomad ASJ AF: 0.198

Gnomad EAS AF: 0.135

Gnomad SAS AF: 0.192

Gnomad FIN AF: 0.163

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.132

Gnomad OTH AF: 0.161

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

GnomAD4 genome AF: 0.159 AC: 24105 AN: 151898 Hom.: 2075 Cov.: 32 AF XY: 0.161 AC XY: 11920 AN XY: 74240

African (AFR) AF: 0.218 AC: 9039 AN: 41430

American (AMR) AF: 0.103 AC: 1574 AN: 15220

Ashkenazi Jewish (ASJ) AF: 0.198 AC: 687 AN: 3464

East Asian (EAS) AF: 0.135 AC: 697 AN: 5168

South Asian (SAS) AF: 0.192 AC: 925 AN: 4816

European-Finnish (FIN) AF: 0.163 AC: 1718 AN: 10564

Middle Eastern (MID) AF: 0.177 AC: 52 AN: 294

European-Non Finnish (NFE) AF: 0.132 AC: 8938 AN: 67924

Other (OTH) AF: 0.167 AC: 352 AN: 2108

Alfa AF: 0.150 Hom.: 303

Bravo AF: 0.156

Asia WGS AF: 0.187 AC: 652 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	5.8
DANN	Benign	0.64
PhyloP100		-0.0040
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: rs11112829; hg19: chr12-79505136;