NM_005639.3:c.-18+40155T>C

Variant names:

• chr12-79087517-T-C
• rs10506807
• NM_005639.3:c.-18+40155T>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+40155T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.152 in 152,084 control chromosomes in the GnomAD database, including 1,870 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 0.15 (1870 hom., cov: 32)
• Consequence: SYT1 NM_005639.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.03
• 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

LOC105369863 (HGNC:):

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 (SAS) allele frequency at 95% confidence interval = 0.187 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+40155T>C		intron	N/A	NP_005630.1	P21579
	SYT1	NM_001135805.2		c.-18+40155T>C		intron	N/A	NP_001129277.1	P21579
	SYT1	NM_001135806.2		c.-18+40155T>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+40155T>C		intron	N/A	ENSP00000261205.4	P21579
	SYT1	ENST00000393240.7	TSL:1	c.-18+40155T>C		intron	N/A	ENSP00000376932.3	P21579
	SYT1	ENST00000552744.5	TSL:1	c.-18+40155T>C		intron	N/A	ENSP00000447575.1	P21579

Frequencies

GnomAD3 genomes AF: 0.151 AC: 22993 AN: 151966 Hom.: 1847 Cov.: 32

Gnomad AFR AF: 0.190

Gnomad AMI AF: 0.135

Gnomad AMR AF: 0.106

Gnomad ASJ AF: 0.194

Gnomad EAS AF: 0.136

Gnomad SAS AF: 0.191

Gnomad FIN AF: 0.164

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.132

Gnomad OTH AF: 0.159

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

GnomAD4 genome AF: 0.152 AC: 23056 AN: 152084 Hom.: 1870 Cov.: 32 AF XY: 0.154 AC XY: 11458 AN XY: 74346

African (AFR) AF: 0.191 AC: 7918 AN: 41500

American (AMR) AF: 0.106 AC: 1611 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.194 AC: 671 AN: 3466

East Asian (EAS) AF: 0.136 AC: 702 AN: 5162

South Asian (SAS) AF: 0.192 AC: 925 AN: 4822

European-Finnish (FIN) AF: 0.164 AC: 1735 AN: 10594

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

European-Non Finnish (NFE) AF: 0.132 AC: 8970 AN: 67970

Other (OTH) AF: 0.165 AC: 349 AN: 2110

Alfa AF: 0.137 Hom.: 6308

Bravo AF: 0.148

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	-0.89
CADD	Benign	0.81
DANN	Benign	0.50
PhyloP100		-1.0
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: rs10506807; hg19: chr12-79481297;