NM_005639.3:c.-84+5006T>C

Variant names:

• chr12-78982937-T-C
• rs10506800
• NM_005639.3:c.-84+5006T>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.-84+5006T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0883 in 152,162 control chromosomes in the GnomAD database, including 762 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 0.088 (762 hom., cov: 32)
• Consequence: SYT1 NM_005639.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.88
• 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.151 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYT1	NM_005639.3	MANE Select	c.-84+5006T>C		intron	N/A	NP_005630.1
	SYT1	NM_001135805.2		c.-84+5006T>C		intron	N/A	NP_001129277.1
	SYT1	NM_001415938.1		c.-18+5006T>C		intron	N/A	NP_001402867.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYT1	ENST00000261205.9	TSL:1 MANE Select	c.-84+5006T>C		intron	N/A	ENSP00000261205.4
	SYT1	ENST00000393240.7	TSL:1	c.-84+5006T>C		intron	N/A	ENSP00000376932.3
	SYT1	ENST00000457153.6	TSL:1	c.-18+5006T>C		intron	N/A	ENSP00000391056.2

Frequencies

GnomAD3 genomes AF: 0.0881 AC: 13395 AN: 152044 Hom.: 751 Cov.: 32

Gnomad AFR AF: 0.153

Gnomad AMI AF: 0.0307

Gnomad AMR AF: 0.106

Gnomad ASJ AF: 0.0829

Gnomad EAS AF: 0.00405

Gnomad SAS AF: 0.0555

Gnomad FIN AF: 0.0583

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0596

Gnomad OTH AF: 0.0717

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

GnomAD4 genome AF: 0.0883 AC: 13439 AN: 152162 Hom.: 762 Cov.: 32 AF XY: 0.0876 AC XY: 6516 AN XY: 74390

African (AFR) AF: 0.154 AC: 6388 AN: 41518

American (AMR) AF: 0.106 AC: 1616 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.0829 AC: 287 AN: 3464

East Asian (EAS) AF: 0.00387 AC: 20 AN: 5170

South Asian (SAS) AF: 0.0551 AC: 266 AN: 4824

European-Finnish (FIN) AF: 0.0583 AC: 618 AN: 10604

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.0596 AC: 4051 AN: 67994

Other (OTH) AF: 0.0738 AC: 156 AN: 2114

Alfa AF: 0.0859 Hom.: 68

Bravo AF: 0.0973

Asia WGS AF: 0.0530 AC: 184 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.090
DANN	Benign	0.45
PhyloP100		-1.9
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: rs10506800; hg19: chr12-79376717;