chr12-79203668-G-T

Variant names:

• chr12-79203668-G-T
• rs1880867
• NM_005639.3:c.-17-13835G>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.-17-13835G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.689 in 151,724 control chromosomes in the GnomAD database, including 36,418 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 0.69 (36418 hom., cov: 32)
• Consequence: SYT1 NM_005639.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0410
• 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: Ambry Genetics, Illumina, G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.714 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYT1	NM_005639.3	c.-17-13835G>T		intron_variant	Intron 3 of 10	ENST00000261205.9	NP_005630.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYT1	ENST00000261205.9	c.-17-13835G>T		intron_variant	Intron 3 of 10	1	NM_005639.3	ENSP00000261205.4

Frequencies

GnomAD3 genomes AF: 0.690 AC: 104561 AN: 151606 Hom.: 36401 Cov.: 32

Gnomad AFR AF: 0.721

Gnomad AMI AF: 0.858

Gnomad AMR AF: 0.725

Gnomad ASJ AF: 0.634

Gnomad EAS AF: 0.425

Gnomad SAS AF: 0.514

Gnomad FIN AF: 0.736

Gnomad MID AF: 0.643

Gnomad NFE AF: 0.689

Gnomad OTH AF: 0.679

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

GnomAD4 genome AF: 0.689 AC: 104610 AN: 151724 Hom.: 36418 Cov.: 32 AF XY: 0.687 AC XY: 50899 AN XY: 74128

African (AFR) AF: 0.720 AC: 29848 AN: 41434

American (AMR) AF: 0.725 AC: 11068 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.634 AC: 2200 AN: 3470

East Asian (EAS) AF: 0.425 AC: 2182 AN: 5136

South Asian (SAS) AF: 0.513 AC: 2459 AN: 4796

European-Finnish (FIN) AF: 0.736 AC: 7738 AN: 10508

Middle Eastern (MID) AF: 0.640 AC: 187 AN: 292

European-Non Finnish (NFE) AF: 0.689 AC: 46737 AN: 67814

Other (OTH) AF: 0.671 AC: 1415 AN: 2110

Alfa AF: 0.695 Hom.: 6443

Bravo AF: 0.694

Asia WGS AF: 0.468 AC: 1627 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	6.1
DANN	Benign	0.81
PhyloP100		0.041
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: rs1880867; hg19: chr12-79597448;