12-79217494-C-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_005639.3(SYT1):c.-17-9C>G variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00861 in 1,553,348 control chromosomes in the GnomAD database, including 84 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0065 (10 hom., cov: 33)
  • Exomes 𝑓: 0.0088 (74 hom.)
• Consequence: SYT1 NM_005639.3 splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.01198
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.105

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BP6: Variant 12-79217494-C-G is Benign according to our data. Variant chr12-79217494-C-G is described in ClinVar as [Benign]. Clinvar id is 2578688.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00651 (992/152288) while in subpopulation NFE AF= 0.00948 (645/68026). AF 95% confidence interval is 0.00888. There are 10 homozygotes in gnomad4. There are 460 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High AC in GnomAd at 992 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SYT1	NM_005639.3	c.-17-9C>G		splice_polypyrimidine_tract_variant, intron_variant		ENST00000261205.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SYT1	ENST00000261205.9	c.-17-9C>G		splice_polypyrimidine_tract_variant, intron_variant		1	NM_005639.3	P3

Frequencies

GnomAD3 genomes AF: 0.00652 AC: 992 AN: 152170 Hom.: 10 Cov.: 33

Gnomad AFR AF: 0.00162

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.00864

Gnomad ASJ AF: 0.0251

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000828

Gnomad FIN AF: 0.00311

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00948

Gnomad OTH AF: 0.00765

GnomAD3 exomes AF: 0.00749 AC: 1531 AN: 204536 Hom.: 15 AF XY: 0.00713 AC XY: 801 AN XY: 112330

Gnomad AFR exome AF: 0.00196

Gnomad AMR exome AF: 0.00894

Gnomad ASJ exome AF: 0.0223

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00178

Gnomad FIN exome AF: 0.00402

Gnomad NFE exome AF: 0.00965

Gnomad OTH exome AF: 0.0130

GnomAD4 exome AF: 0.00884 AC: 12386 AN: 1401060 Hom.: 74 Cov.: 28 AF XY: 0.00868 AC XY: 6041 AN XY: 695804

Gnomad4 AFR exome AF: 0.00147

Gnomad4 AMR exome AF: 0.00862

Gnomad4 ASJ exome AF: 0.0223

Gnomad4 EAS exome AF: 0.0000265

Gnomad4 SAS exome AF: 0.00185

Gnomad4 FIN exome AF: 0.00489

Gnomad4 NFE exome AF: 0.00972

Gnomad4 OTH exome AF: 0.00988

GnomAD4 genome AF: 0.00651 AC: 992 AN: 152288 Hom.: 10 Cov.: 33 AF XY: 0.00618 AC XY: 460 AN XY: 74474

Gnomad4 AFR AF: 0.00161

Gnomad4 AMR AF: 0.00856

Gnomad4 ASJ AF: 0.0251

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000829

Gnomad4 FIN AF: 0.00311

Gnomad4 NFE AF: 0.00948

Gnomad4 OTH AF: 0.00757

Alfa AF: 0.00592 Hom.: 2

Bravo AF: 0.00666

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Apr 01, 2024

SYT1: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
Cadd	Benign	15
Dann	Benign	0.71

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.012
dbscSNV1_RF	Benign	0.092
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

Publications

LitVar

Other links and lift over

dbSNP: rs151296432; hg19: chr12-79611274;