Variant chr12-79292133-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_005639.3(SYT1):c.474+3C>A variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.363 in 1,609,632 control chromosomes in the GnomAD database, including 108,470 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.36 ( 9950 hom., cov: 32)

Exomes 𝑓: 0.36 ( 98520 hom. )

Consequence

SYT1
NM_005639.3 splice_donor_region, intron

Scores

Splicing: ADA: 0.0005512

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.466

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.35).

BP6

Variant 12-79292133-C-A is Benign according to our data. Variant chr12-79292133-C-A is described in ClinVar as [Benign]. Clinvar id is 1334917.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.568 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SYT1	NM_005639.3 linkuse as main transcript	c.474+3C>A		splice_donor_region_variant, intron_variant		ENST00000261205.9	NP_005630.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SYT1	ENST00000261205.9 linkuse as main transcript	c.474+3C>A		splice_donor_region_variant, intron_variant		1	NM_005639.3	ENSP00000261205	P3

Frequencies

GnomAD3 genomes

AF:

0.356

AC:

54112

AN:

151922

Hom.:

9922

Cov.:

show subpopulations

Gnomad AFR

AF:

0.339

Gnomad AMI

AF:

0.158

Gnomad AMR

AF:

0.301

Gnomad ASJ

AF:

0.420

Gnomad EAS

AF:

0.585

Gnomad SAS

AF:

0.470

Gnomad FIN

AF:

0.312

Gnomad MID

AF:

0.408

Gnomad NFE

AF:

0.359

Gnomad OTH

AF:

0.363

GnomAD3 exomes

AF:

0.372

AC:

92764

AN:

249124

Hom.:

18238

AF XY:

0.381

AC XY:

51307

AN XY:

134662

show subpopulations

Gnomad AFR exome

AF:

0.343

Gnomad AMR exome

AF:

0.263

Gnomad ASJ exome

AF:

0.423

Gnomad EAS exome

AF:

0.592

Gnomad SAS exome

AF:

0.468

Gnomad FIN exome

AF:

0.319

Gnomad NFE exome

AF:

0.354

Gnomad OTH exome

AF:

0.382

GnomAD4 exome

AF:

0.363

AC:

529407

AN:

1457590

Hom.:

98520

Cov.:

AF XY:

0.367

AC XY:

266058

AN XY:

725212

show subpopulations

Gnomad4 AFR exome

AF:

0.329

Gnomad4 AMR exome

AF:

0.268

Gnomad4 ASJ exome

AF:

0.425

Gnomad4 EAS exome

AF:

0.580

Gnomad4 SAS exome

AF:

0.463

Gnomad4 FIN exome

AF:

0.324

Gnomad4 NFE exome

AF:

0.352

Gnomad4 OTH exome

AF:

0.380

GnomAD4 genome

AF:

0.356

AC:

54180

AN:

152042

Hom.:

9950

Cov.:

AF XY:

0.357

AC XY:

26548

AN XY:

74306

show subpopulations

Gnomad4 AFR

AF:

0.339

Gnomad4 AMR

AF:

0.301

Gnomad4 ASJ

AF:

0.420

Gnomad4 EAS

AF:

0.585

Gnomad4 SAS

AF:

0.471

Gnomad4 FIN

AF:

0.312

Gnomad4 NFE

AF:

0.359

Gnomad4 OTH

AF:

0.372

Alfa

AF:

0.357

Hom.:

21840

Bravo

AF:

0.350

Asia WGS

AF:

0.533

AC:

1850

AN:

3478

EpiCase

AF:

0.362

EpiControl

AF:

0.357

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

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

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

SYT1-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 21, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.35

CADD

Benign

DANN

Benign

0.83

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00055

dbscSNV1_RF

Benign

0.080

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over