rs76502784

chr21-32699829-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_203446.3(SYNJ1):c.479+9A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0449 in 1,603,016 control chromosomes in the GnomAD database, including 1,822 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.034 (110 hom., cov: 32)
  • Exomes 𝑓: 0.046 (1712 hom.)
• Consequence: SYNJ1 NM_203446.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.30

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 21-32699829-T-C is Benign according to our data. Variant chr21-32699829-T-C is described in ClinVar as [Benign]. Clinvar id is 478364.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.069 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SYNJ1	NM_203446.3	c.479+9A>G		intron_variant		ENST00000674351.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SYNJ1	ENST00000674351.1	c.479+9A>G		intron_variant			NM_203446.3

Frequencies

GnomAD3 genomes AF: 0.0336 AC: 5111 AN: 152008 Hom.: 110 Cov.: 32

Gnomad AFR AF: 0.0156

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0211

Gnomad ASJ AF: 0.0179

Gnomad EAS AF: 0.0750

Gnomad SAS AF: 0.0357

Gnomad FIN AF: 0.0314

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0462

Gnomad OTH AF: 0.0244

GnomAD3 exomes AF: 0.0377 AC: 9181 AN: 243770 Hom.: 194 AF XY: 0.0379 AC XY: 4999 AN XY: 132068

Gnomad AFR exome AF: 0.0155

Gnomad AMR exome AF: 0.0132

Gnomad ASJ exome AF: 0.0190

Gnomad EAS exome AF: 0.0746

Gnomad SAS exome AF: 0.0366

Gnomad FIN exome AF: 0.0380

Gnomad NFE exome AF: 0.0440

Gnomad OTH exome AF: 0.0356

GnomAD4 exome AF: 0.0461 AC: 66837 AN: 1450890 Hom.: 1712 Cov.: 31 AF XY: 0.0455 AC XY: 32825 AN XY: 720824

Gnomad4 AFR exome AF: 0.0142

Gnomad4 AMR exome AF: 0.0134

Gnomad4 ASJ exome AF: 0.0192

Gnomad4 EAS exome AF: 0.0706

Gnomad4 SAS exome AF: 0.0363

Gnomad4 FIN exome AF: 0.0373

Gnomad4 NFE exome AF: 0.0497

Gnomad4 OTH exome AF: 0.0398

GnomAD4 genome AF: 0.0336 AC: 5107 AN: 152126 Hom.: 110 Cov.: 32 AF XY: 0.0328 AC XY: 2439 AN XY: 74360

Gnomad4 AFR AF: 0.0155

Gnomad4 AMR AF: 0.0211

Gnomad4 ASJ AF: 0.0179

Gnomad4 EAS AF: 0.0751

Gnomad4 SAS AF: 0.0353

Gnomad4 FIN AF: 0.0314

Gnomad4 NFE AF: 0.0462

Gnomad4 OTH AF: 0.0242

Alfa AF: 0.0388 Hom.: 63

Bravo AF: 0.0316

Asia WGS AF: 0.0480 AC: 169 AN: 3478

EpiCase AF: 0.0405

EpiControl AF: 0.0408

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Early-onset Parkinson disease 20;C4479313:Developmental and epileptic encephalopathy, 53 Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Athena Diagnostics

Aug 09, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
Cadd	Benign	1.5
Dann	Benign	0.65
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs76502784; hg19: chr21-34072139;