rs2833930

chr21-32642458-C-T

Variant summary

Our verdict is Benign. Variant got -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

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 -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SYNJ1	NM_203446.3	c.3479-325G>A		intron_variant		ENST00000674351.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SYNJ1	ENST00000674351.1	c.3479-325G>A		intron_variant			NM_203446.3

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

Gnomad4 AFR AF: 0.299

Gnomad4 AMR AF: 0.280

Gnomad4 ASJ AF: 0.398

Gnomad4 EAS AF: 0.346

Gnomad4 SAS AF: 0.314

Gnomad4 FIN AF: 0.227

Gnomad4 NFE AF: 0.286

Gnomad4 OTH AF: 0.317

Alfa AF: 0.294 Hom.: 11283

Bravo AF: 0.296

Asia WGS AF: 0.300 AC: 1044 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	4.7
Dann	Benign	0.51

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

Publications

LitVar

Other links and lift over

dbSNP: rs2833930; hg19: chr21-34014768;