dbSNP rs844996: SYNJ1:c.1811+1072G>A (chr21-32669216-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_203446.3(SYNJ1):c.1811+1072G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.913 in 152,252 control chromosomes in the GnomAD database, including 63,484 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 0.91 ( 63484 hom., cov: 32)

Consequence

SYNJ1
NM_203446.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.817

Publications

8 publications found

Variant links:

Genes affected

SYNJ1 (HGNC:11503): (synaptojanin 1) This gene encodes a phosphoinositide phosphatase that regulates levels of membrane phosphatidylinositol-4,5-bisphosphate. As such, expression of this enzyme may affect synaptic transmission and membrane trafficking. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2011]

SYNJ1 Gene-Disease associations (from GenCC):

genetic developmental and epileptic encephalopathy
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
developmental and epileptic encephalopathy, 53
Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
early-onset Parkinson disease 20
Inheritance: AR Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Genomics England PanelApp
undetermined early-onset epileptic encephalopathy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
atypical juvenile parkinsonism
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
young-onset Parkinson disease
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

SYNJ1 links:

Genome browser will be placed here

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=-0.9).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.97 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYNJ1	NM_203446.3 link	c.1811+1072G>A		intron_variant	Intron 15 of 32	ENST00000674351.1	NP_982271.3	O43426-2C9JFZ1Q05CZ1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYNJ1	ENST00000674351.1 link	c.1811+1072G>A		intron_variant	Intron 15 of 32		NM_203446.3	ENSP00000501530.1		O43426-2

Frequencies

GnomAD3 genomes

AF:

0.913

AC:

138864

AN:

152134

Hom.:

63435

Cov.:

show subpopulations

Gnomad AFR

AF:

0.927

Gnomad AMI

AF:

0.918

Gnomad AMR

AF:

0.906

Gnomad ASJ

AF:

0.925

Gnomad EAS

AF:

0.992

Gnomad SAS

AF:

0.934

Gnomad FIN

AF:

0.904

Gnomad MID

AF:

0.905

Gnomad NFE

AF:

0.899

Gnomad OTH

AF:

0.896

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

GnomAD4 genome

AF:

0.913

AC:

138972

AN:

152252

Hom.:

63484

Cov.:

AF XY:

0.914

AC XY:

68053

AN XY:

74444

show subpopulations

African (AFR)

AF:

0.927

AC:

38514

AN:

41542

American (AMR)

AF:

0.906

AC:

13851

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.925

AC:

3211

AN:

3472

East Asian (EAS)

AF:

0.992

AC:

5145

AN:

5184

South Asian (SAS)

AF:

0.934

AC:

4504

AN:

4824

European-Finnish (FIN)

AF:

0.904

AC:

9582

AN:

10602

Middle Eastern (MID)

AF:

0.912

AC:

268

AN:

294

European-Non Finnish (NFE)

AF:

0.899

AC:

61161

AN:

68014

Other (OTH)

AF:

0.897

AC:

1899

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

631

1262

1894

2525

3156

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

908

1816

2724

3632

4540

<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:

0.907

Hom.:

115997

Bravo

AF:

0.916

Asia WGS

AF:

0.970

AC:

3373

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

5.3

(source)

DANN

Benign

0.55

PhyloP100

0.82

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over