Genetic Variant SYT1:c.-18+14778T>C (chr12-79062140-T-C) – 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+14778T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.208 in 152,010 control chromosomes in the GnomAD database, including 3,753 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 0.21 ( 3753 hom., cov: 32)

Consequence

SYT1
NM_005639.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.42

Publications

1 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: Labcorp Genetics (formerly Invitae), Illumina, PanelApp Australia, Ambry Genetics, G2P

SYT1 links:

LOC105369863 (HGNC:):

LOC105369863 links:

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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=-0.83).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.309 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+14778T>C	intron	N/A	NP_005630.1	P21579
SYT1	NM_001135805.2		c.-18+14778T>C	intron	N/A	NP_001129277.1	P21579
SYT1	NM_001135806.2		c.-18+14778T>C	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+14778T>C	intron	N/A	ENSP00000261205.4	P21579
SYT1	ENST00000393240.7	TSL:1	c.-18+14778T>C	intron	N/A	ENSP00000376932.3	P21579
SYT1	ENST00000552744.5	TSL:1	c.-18+14778T>C	intron	N/A	ENSP00000447575.1	P21579

Frequencies

GnomAD3 genomes

AF:

0.208

AC:

31533

AN:

151892

Hom.:

3717

Cov.:

show subpopulations

Gnomad AFR

AF:

0.313

Gnomad AMI

AF:

0.0384

Gnomad AMR

AF:

0.247

Gnomad ASJ

AF:

0.187

Gnomad EAS

AF:

0.308

Gnomad SAS

AF:

0.241

Gnomad FIN

AF:

0.123

Gnomad MID

AF:

0.149

Gnomad NFE

AF:

0.142

Gnomad OTH

AF:

0.195

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

GnomAD4 genome

AF:

0.208

AC:

31631

AN:

152010

Hom.:

3753

Cov.:

AF XY:

0.210

AC XY:

15595

AN XY:

74344

show subpopulations

African (AFR)

AF:

0.314

AC:

13005

AN:

41430

American (AMR)

AF:

0.248

AC:

3781

AN:

15240

Ashkenazi Jewish (ASJ)

AF:

0.187

AC:

648

AN:

3472

East Asian (EAS)

AF:

0.307

AC:

1583

AN:

5150

South Asian (SAS)

AF:

0.241

AC:

1163

AN:

4824

European-Finnish (FIN)

AF:

0.123

AC:

1302

AN:

10596

Middle Eastern (MID)

AF:

0.139

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.142

AC:

9651

AN:

67988

Other (OTH)

AF:

0.201

AC:

422

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

1257

2514

3772

5029

6286

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

322

644

966

1288

1610

<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:

0.183

Hom.:

386

Bravo

AF:

0.225

Asia WGS

AF:

0.268

AC:

934

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

5.4

(source)

DANN

Benign

0.76

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

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