12-79217594-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Moderate BP6_Moderate BP7 BA1

The NM_005639.3(SYT1):c.75C>T(p.Asn25=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.684 in 1,611,476 control chromosomes in the GnomAD database, including 380,877 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.71 (38334 hom., cov: 32)
  • Exomes 𝑓: 0.68 (342543 hom.)
• Consequence: SYT1 NM_005639.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0710

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BP6: Variant 12-79217594-C-T is Benign according to our data. Variant chr12-79217594-C-T is described in ClinVar as [Benign]. Clinvar id is 1334916.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.071 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.768 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SYT1	NM_005639.3	c.75C>T	p.Asn25=	synonymous_variant	4/11	ENST00000261205.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SYT1	ENST00000261205.9	c.75C>T	p.Asn25=	synonymous_variant	4/11	1	NM_005639.3	P3

Frequencies

GnomAD3 genomes AF: 0.705 AC: 107182 AN: 151928 Hom.: 38315 Cov.: 32

Gnomad AFR AF: 0.776

Gnomad AMI AF: 0.860

Gnomad AMR AF: 0.731

Gnomad ASJ AF: 0.634

Gnomad EAS AF: 0.427

Gnomad SAS AF: 0.504

Gnomad FIN AF: 0.738

Gnomad MID AF: 0.639

Gnomad NFE AF: 0.690

Gnomad OTH AF: 0.688

GnomAD3 exomes AF: 0.666 AC: 165715 AN: 248724 Hom.: 56779 AF XY: 0.655 AC XY: 88082 AN XY: 134528

Gnomad AFR exome AF: 0.775

Gnomad AMR exome AF: 0.758

Gnomad ASJ exome AF: 0.631

Gnomad EAS exome AF: 0.413

Gnomad SAS exome AF: 0.513

Gnomad FIN exome AF: 0.732

Gnomad NFE exome AF: 0.696

Gnomad OTH exome AF: 0.661

GnomAD4 exome AF: 0.681 AC: 994583 AN: 1459430 Hom.: 342543 Cov.: 55 AF XY: 0.676 AC XY: 490481 AN XY: 726012

Gnomad4 AFR exome AF: 0.784

Gnomad4 AMR exome AF: 0.756

Gnomad4 ASJ exome AF: 0.632

Gnomad4 EAS exome AF: 0.443

Gnomad4 SAS exome AF: 0.517

Gnomad4 FIN exome AF: 0.730

Gnomad4 NFE exome AF: 0.697

Gnomad4 OTH exome AF: 0.662

GnomAD4 genome AF: 0.705 AC: 107236 AN: 152046 Hom.: 38334 Cov.: 32 AF XY: 0.702 AC XY: 52146 AN XY: 74300

Gnomad4 AFR AF: 0.776

Gnomad4 AMR AF: 0.731

Gnomad4 ASJ AF: 0.634

Gnomad4 EAS AF: 0.427

Gnomad4 SAS AF: 0.503

Gnomad4 FIN AF: 0.738

Gnomad4 NFE AF: 0.690

Gnomad4 OTH AF: 0.679

Alfa AF: 0.692 Hom.: 14965

Bravo AF: 0.712

Asia WGS AF: 0.467 AC: 1628 AN: 3478

EpiCase AF: 0.683

EpiControl AF: 0.688

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Infantile hypotonia-oculomotor anomalies-hyperkinetic movements-developmental delay syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 15, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
Cadd	Benign	1.5
Dann	Benign	0.83

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

Publications

LitVar

Other links and lift over

dbSNP: rs2037743; hg19: chr12-79611374; COSMIC: COSV54031209; COSMIC: COSV54031209;