rs864603

Variant names:

• chr21-32648603-C-T
• rs864603
• NM_203446.3:c.3037+1581G>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.3037+1581G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0799 in 152,216 control chromosomes in the GnomAD database, including 632 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 0.080 (632 hom., cov: 32)
• Consequence: SYNJ1 NM_203446.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.35
• 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
• 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.147 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYNJ1	NM_203446.3	c.3037+1581G>A		intron_variant	Intron 23 of 32	ENST00000674351.1	NP_982271.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYNJ1	ENST00000674351.1	c.3037+1581G>A		intron_variant	Intron 23 of 32		NM_203446.3	ENSP00000501530.1

Frequencies

GnomAD3 genomes AF: 0.0799 AC: 12159 AN: 152098 Hom.: 632 Cov.: 32

Gnomad AFR AF: 0.130

Gnomad AMI AF: 0.140

Gnomad AMR AF: 0.0510

Gnomad ASJ AF: 0.0861

Gnomad EAS AF: 0.0712

Gnomad SAS AF: 0.155

Gnomad FIN AF: 0.0237

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.0587

Gnomad OTH AF: 0.0848

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

GnomAD4 genome AF: 0.0799 AC: 12168 AN: 152216 Hom.: 632 Cov.: 32 AF XY: 0.0800 AC XY: 5952 AN XY: 74428

African (AFR) AF: 0.130 AC: 5383 AN: 41500

American (AMR) AF: 0.0509 AC: 778 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0861 AC: 299 AN: 3472

East Asian (EAS) AF: 0.0702 AC: 364 AN: 5184

South Asian (SAS) AF: 0.156 AC: 752 AN: 4828

European-Finnish (FIN) AF: 0.0237 AC: 251 AN: 10608

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.0586 AC: 3987 AN: 68014

Other (OTH) AF: 0.0896 AC: 189 AN: 2110

Alfa AF: 0.0746 Hom.: 69

Bravo AF: 0.0808

Asia WGS AF: 0.156 AC: 542 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.10
DANN	Benign	0.51
PhyloP100		-1.3
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs864603; hg19: chr21-34020913;