dbSNP rs1033196: SYT1:c.-18+1695G>A (chr12-79049057-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_005639.3(SYT1):c.-18+1695G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.199 in 151,672 control chromosomes in the GnomAD database, including 3,357 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.20 ( 3357 hom., cov: 32)

Consequence

SYT1
NM_005639.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.40

Publications

3 publications found

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 Gene-Disease associations (from GenCC):

infantile hypotonia-oculomotor anomalies-hyperkinetic movements-developmental delay syndrome
Inheritance: AD Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P, Illumina, PanelApp Australia

SYT1 links:

LOC105369863 (HGNC:):

LOC105369863 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_005639.3, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.97).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.294 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005639.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SYT1	NM_005639.3	MANE Select	c.-18+1695G>A	intron	N/A	NP_005630.1	P21579
SYT1	NM_001135805.2		c.-18+1695G>A	intron	N/A	NP_001129277.1	P21579
SYT1	NM_001135806.2		c.-18+1695G>A	intron	N/A	NP_001129278.1	P21579

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SYT1	ENST00000261205.9	TSL:1 MANE Select	c.-18+1695G>A	intron	N/A	ENSP00000261205.4	P21579
SYT1	ENST00000393240.7	TSL:1	c.-18+1695G>A	intron	N/A	ENSP00000376932.3	P21579
SYT1	ENST00000552744.5	TSL:1	c.-18+1695G>A	intron	N/A	ENSP00000447575.1	P21579

Frequencies

GnomAD3 genomes

AF:

0.199

AC:

30162

AN:

151554

Hom.:

3320

Cov.:

show subpopulations

Gnomad AFR

AF:

0.283

Gnomad AMI

AF:

0.0384

Gnomad AMR

AF:

0.246

Gnomad ASJ

AF:

0.187

Gnomad EAS

AF:

0.307

Gnomad SAS

AF:

0.240

Gnomad FIN

AF:

0.123

Gnomad MID

AF:

0.146

Gnomad NFE

AF:

0.142

Gnomad OTH

AF:

0.190

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.199

AC:

30257

AN:

151672

Hom.:

3357

Cov.:

AF XY:

0.202

AC XY:

14951

AN XY:

74112

show subpopulations

African (AFR)

AF:

0.284

AC:

11747

AN:

41402

American (AMR)

AF:

0.247

AC:

3749

AN:

15202

Ashkenazi Jewish (ASJ)

AF:

0.187

AC:

648

AN:

3464

East Asian (EAS)

AF:

0.307

AC:

1579

AN:

5146

South Asian (SAS)

AF:

0.241

AC:

1158

AN:

4812

European-Finnish (FIN)

AF:

0.123

AC:

1297

AN:

10570

Middle Eastern (MID)

AF:

0.136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.142

AC:

9590

AN:

67758

Other (OTH)

AF:

0.196

AC:

414

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1227

2454

3681

4908

6135

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

312

624

936

1248

1560

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.166

Hom.:

1277

Bravo

AF:

0.215

Asia WGS

AF:

0.265

AC:

922

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.97

CADD

Benign

0.013

(source)

DANN

Benign

0.39

PhyloP100

-1.4

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over