Variant chr12-79217494-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

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 Likely 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

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.105

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 -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 [Likely_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 GnomAd4 at 992 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SYT1	NM_005639.3 linkuse as main transcript	c.-17-9C>G		splice_polypyrimidine_tract_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.-17-9C>G		splice_polypyrimidine_tract_variant, intron_variant		1	NM_005639.3	ENSP00000261205	P3

Frequencies

GnomAD3 genomes

AF:

0.00652

AC:

992

AN:

152170

Hom.:

Cov.:

show subpopulations

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.:

AF XY:

0.00713

AC XY:

801

AN XY:

112330

show subpopulations

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.:

Cov.:

AF XY:

0.00868

AC XY:

6041

AN XY:

695804

show subpopulations

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.:

Cov.:

AF XY:

0.00618

AC XY:

460

AN XY:

74474

show subpopulations

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.:

Bravo

AF:

0.00666

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Aug 01, 2024

SYT1: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.63

CADD

Benign

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

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