rs11838060

Variant names:

• chr12-79079879-G-T
• rs11838060
• NM_005639.3:c.-18+32517G>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+32517G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.157 in 151,918 control chromosomes in the GnomAD database, including 2,083 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 (2083 hom., cov: 32)
• Consequence: SYT1 NM_005639.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.486
• Publications: 5 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)

LOC105369863 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.212 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYT1	NM_005639.3	c.-18+32517G>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.-18+32517G>T		intron_variant	Intron 3 of 10	1	NM_005639.3	ENSP00000261205.4

Frequencies

GnomAD3 genomes AF: 0.157 AC: 23849 AN: 151800 Hom.: 2068 Cov.: 32

Gnomad AFR AF: 0.215

Gnomad AMI AF: 0.109

Gnomad AMR AF: 0.131

Gnomad ASJ AF: 0.217

Gnomad EAS AF: 0.0328

Gnomad SAS AF: 0.123

Gnomad FIN AF: 0.109

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.144

Gnomad OTH AF: 0.164

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

GnomAD4 genome AF: 0.157 AC: 23904 AN: 151918 Hom.: 2083 Cov.: 32 AF XY: 0.154 AC XY: 11439 AN XY: 74262

African (AFR) AF: 0.216 AC: 8942 AN: 41432

American (AMR) AF: 0.130 AC: 1990 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.217 AC: 751 AN: 3468

East Asian (EAS) AF: 0.0328 AC: 170 AN: 5178

South Asian (SAS) AF: 0.124 AC: 596 AN: 4820

European-Finnish (FIN) AF: 0.109 AC: 1149 AN: 10562

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.144 AC: 9801 AN: 67894

Other (OTH) AF: 0.163 AC: 343 AN: 2106

Alfa AF: 0.142 Hom.: 1977

Bravo AF: 0.162

Asia WGS AF: 0.0990 AC: 343 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.064
DANN	Benign	0.25
PhyloP100		-0.49
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: rs11838060; hg19: chr12-79473659;