chr21-32645668-T-C

Variant names:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_203446.3(SYNJ1):c.3369A>G(p.Pro1123Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00289 in 1,525,346 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0018 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0030 ( 9 hom. )

Consequence

SYNJ1
NM_203446.3 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -0.223

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.6).

BP6

Variant 21-32645668-T-C is Benign according to our data. Variant chr21-32645668-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 478341.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-32645668-T-C is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=-0.223 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00178 (271/151950) while in subpopulation NFE AF= 0.00328 (223/67926). AF 95% confidence interval is 0.00293. There are 0 homozygotes in gnomad4. There are 129 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYNJ1	NM_203446.3 link	c.3369A>G	p.Pro1123Pro	synonymous_variant	Exon 25 of 33	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.3369A>G	p.Pro1123Pro	synonymous_variant	Exon 25 of 33		NM_203446.3	ENSP00000501530.1		O43426-2

Frequencies

GnomAD3 genomes

AF:

0.00178

AC:

271

AN:

151834

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000508

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00111

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000945

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00328

Gnomad OTH

AF:

0.00240

GnomAD3 exomes

AF:

0.00154

AC:

209

AN:

135914

Hom.:

AF XY:

0.00154

AC XY:

112

AN XY:

72838

show subpopulations

Gnomad AFR exome

AF:

0.000332

Gnomad AMR exome

AF:

0.00142

Gnomad ASJ exome

AF:

0.00166

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000630

Gnomad FIN exome

AF:

0.000141

Gnomad NFE exome

AF:

0.00276

Gnomad OTH exome

AF:

0.00146

GnomAD4 exome

AF:

0.00301

AC:

4131

AN:

1373396

Hom.:

Cov.:

AF XY:

0.00288

AC XY:

1951

AN XY:

677280

show subpopulations

Gnomad4 AFR exome

AF:

0.000332

Gnomad4 AMR exome

AF:

0.00138

Gnomad4 ASJ exome

AF:

0.00161

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000138

Gnomad4 FIN exome

AF:

0.000267

Gnomad4 NFE exome

AF:

0.00367

Gnomad4 OTH exome

AF:

0.00166

GnomAD4 genome

AF:

0.00178

AC:

271

AN:

151950

Hom.:

Cov.:

AF XY:

0.00174

AC XY:

129

AN XY:

74292

show subpopulations

Gnomad4 AFR

AF:

0.000507

Gnomad4 AMR

AF:

0.00111

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000945

Gnomad4 NFE

AF:

0.00328

Gnomad4 OTH

AF:

0.00238

Alfa

AF:

0.00133

Hom.:

Bravo

AF:

0.00205

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Jan 09, 2021

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Sep 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

SYNJ1: BP4, BP7 -

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not specified

Benign:1

Sep 14, 2020

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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

Benign:1

Jan 27, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

SYNJ1-related disorder

Benign:1

Apr 05, 2019

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.60

CADD

Benign

5.0

DANN

Benign

0.56

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over