Variant 12-79217594-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.0710

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 -19 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_multiple_submitters_no_conflicts, 2 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	Protein	UniProt
SYT1	NM_005639.3 linkuse as main transcript	c.75C>T	p.Asn25=	synonymous_variant	4/11	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.75C>T	p.Asn25=	synonymous_variant	4/11	1	NM_005639.3	ENSP00000261205	P3

Frequencies

GnomAD3 genomes

AF:

0.705

AC:

107182

AN:

151928

Hom.:

38315

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.676

AC XY:

490481

AN XY:

726012

show subpopulations

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.:

AF XY:

0.702

AC XY:

52146

AN XY:

74300

show subpopulations

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:2

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

- -

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

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