chr12-79095238-C-T

Variant names:

• chr12-79095238-C-T
• rs7972593
• NM_005639.3:c.-18+47876C>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+47876C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.11 in 151,802 control chromosomes in the GnomAD database, including 988 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 0.11 (988 hom., cov: 32)
• Consequence: SYT1 NM_005639.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.305
• Publications: 2 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.12 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+47876C>T		intron	N/A	NP_005630.1	P21579
	SYT1	NM_001135805.2		c.-18+47876C>T		intron	N/A	NP_001129277.1	P21579
	SYT1	NM_001135806.2		c.-18+47876C>T		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+47876C>T		intron	N/A	ENSP00000261205.4	P21579
	SYT1	ENST00000393240.7	TSL:1	c.-18+47876C>T		intron	N/A	ENSP00000376932.3	P21579
	SYT1	ENST00000552744.5	TSL:1	c.-18+47876C>T		intron	N/A	ENSP00000447575.1	P21579

Frequencies

GnomAD3 genomes AF: 0.110 AC: 16705 AN: 151684 Hom.: 985 Cov.: 32

Gnomad AFR AF: 0.122

Gnomad AMI AF: 0.107

Gnomad AMR AF: 0.0836

Gnomad ASJ AF: 0.178

Gnomad EAS AF: 0.0309

Gnomad SAS AF: 0.0818

Gnomad FIN AF: 0.0779

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.118

Gnomad OTH AF: 0.119

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

GnomAD4 genome AF: 0.110 AC: 16731 AN: 151802 Hom.: 988 Cov.: 32 AF XY: 0.107 AC XY: 7963 AN XY: 74212

African (AFR) AF: 0.123 AC: 5080 AN: 41438

American (AMR) AF: 0.0834 AC: 1269 AN: 15216

Ashkenazi Jewish (ASJ) AF: 0.178 AC: 617 AN: 3464

East Asian (EAS) AF: 0.0310 AC: 160 AN: 5162

South Asian (SAS) AF: 0.0821 AC: 396 AN: 4822

European-Finnish (FIN) AF: 0.0779 AC: 822 AN: 10554

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

European-Non Finnish (NFE) AF: 0.118 AC: 8006 AN: 67836

Other (OTH) AF: 0.118 AC: 248 AN: 2104

Alfa AF: 0.116 Hom.: 548

Bravo AF: 0.111

Asia WGS AF: 0.0580 AC: 203 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	7.6
DANN	Benign	0.68
PhyloP100		0.30
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: rs7972593; hg19: chr12-79489018;