rs2833930

Variant names:

• chr21-32642458-C-T
• rs2833930
• NM_203446.3:c.3479-325G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_203446.3(SYNJ1):​c.3479-325G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.291 in 152,120 control chromosomes in the GnomAD database, including 6,492 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 0.29 (6492 hom., cov: 32)
• Consequence: SYNJ1 NM_203446.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.227
• Publications: 3 publications found

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, PanelApp Australia
• early-onset Parkinson disease 20

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Genomics England PanelApp, PanelApp Australia
• 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.333 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_203446.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYNJ1	NM_203446.3	MANE Select	c.3479-325G>A		intron	N/A	NP_982271.3	O43426-2
	SYNJ1	NM_003895.4		c.3596-325G>A		intron	N/A	NP_003886.3
	SYNJ1	NM_001160306.2		c.3377-492G>A		intron	N/A	NP_001153778.1	A0A0D9SGJ6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYNJ1	ENST00000674351.1	MANE Select	c.3479-325G>A		intron	N/A	ENSP00000501530.1	O43426-2
	SYNJ1	ENST00000630077.3	TSL:1	c.3377-492G>A		intron	N/A	ENSP00000487560.1	A0A0D9SGJ6
	SYNJ1	ENST00000674308.1		c.3479-325G>A		intron	N/A	ENSP00000501426.1	O43426-1

Frequencies

GnomAD3 genomes AF: 0.291 AC: 44180 AN: 152000 Hom.: 6485 Cov.: 32

Gnomad AFR AF: 0.300

Gnomad AMI AF: 0.245

Gnomad AMR AF: 0.280

Gnomad ASJ AF: 0.398

Gnomad EAS AF: 0.346

Gnomad SAS AF: 0.314

Gnomad FIN AF: 0.227

Gnomad MID AF: 0.369

Gnomad NFE AF: 0.286

Gnomad OTH AF: 0.316

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

GnomAD4 genome AF: 0.291 AC: 44206 AN: 152120 Hom.: 6492 Cov.: 32 AF XY: 0.290 AC XY: 21534 AN XY: 74342

African (AFR) AF: 0.299 AC: 12423 AN: 41488

American (AMR) AF: 0.280 AC: 4284 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.398 AC: 1381 AN: 3468

East Asian (EAS) AF: 0.346 AC: 1789 AN: 5172

South Asian (SAS) AF: 0.314 AC: 1510 AN: 4814

European-Finnish (FIN) AF: 0.227 AC: 2398 AN: 10574

Middle Eastern (MID) AF: 0.356 AC: 104 AN: 292

European-Non Finnish (NFE) AF: 0.286 AC: 19428 AN: 68006

Other (OTH) AF: 0.317 AC: 666 AN: 2104

Alfa AF: 0.293 Hom.: 17349

Bravo AF: 0.296

Asia WGS AF: 0.300 AC: 1044 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.7
DANN	Benign	0.51
PhyloP100		-0.23
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2833930; hg19: chr21-34014768;