Variant chr21-32695050-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_203446.3(SYNJ1):c.705+7A>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00147 in 1,613,046 control chromosomes in the GnomAD database, including 40 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.00093 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0015 ( 39 hom. )

Consequence

SYNJ1
NM_203446.3 splice_region, intron

Scores

Splicing: ADA: 0.00005055

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.213

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.71).

BP6

Variant 21-32695050-T-C is Benign according to our data. Variant chr21-32695050-T-C is described in ClinVar as [Benign]. Clinvar id is 478366.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-32695050-T-C is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000932 (142/152350) while in subpopulation SAS AF= 0.0168 (81/4830). AF 95% confidence interval is 0.0138. There are 1 homozygotes in gnomad4. There are 87 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 39 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SYNJ1	NM_203446.3 linkuse as main transcript	c.705+7A>G		splice_region_variant, intron_variant		ENST00000674351.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SYNJ1	ENST00000674351.1 linkuse as main transcript	c.705+7A>G		splice_region_variant, intron_variant			NM_203446.3		O43426-2

Frequencies

GnomAD3 genomes

AF:

0.000939

AC:

143

AN:

152232

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000338

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00118

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.0170

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000353

Gnomad OTH

AF:

0.000955

GnomAD3 exomes

AF:

0.00277

AC:

696

AN:

251006

Hom.:

AF XY:

0.00371

AC XY:

504

AN XY:

135738

show subpopulations

Gnomad AFR exome

AF:

0.000247

Gnomad AMR exome

AF:

0.000260

Gnomad ASJ exome

AF:

0.0000993

Gnomad EAS exome

AF:

0.000218

Gnomad SAS exome

AF:

0.0196

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000564

Gnomad OTH exome

AF:

0.00245

GnomAD4 exome

AF:

0.00152

AC:

2224

AN:

1460696

Hom.:

Cov.:

AF XY:

0.00212

AC XY:

1541

AN XY:

726758

show subpopulations

Gnomad4 AFR exome

AF:

0.000478

Gnomad4 AMR exome

AF:

0.000268

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.0193

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000311

Gnomad4 OTH exome

AF:

0.00189

GnomAD4 genome

AF:

0.000932

AC:

142

AN:

152350

Hom.:

Cov.:

AF XY:

0.00117

AC XY:

AN XY:

74512

show subpopulations

Gnomad4 AFR

AF:

0.000337

Gnomad4 AMR

AF:

0.00118

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.0168

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000353

Gnomad4 OTH

AF:

0.000945

Alfa

AF:

0.000690

Hom.:

Bravo

AF:

0.000597

Asia WGS

AF:

0.00433

AC:

AN:

3478

EpiCase

AF:

0.000273

EpiControl

AF:

0.000830

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

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

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 25, 2024

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Athena Diagnostics

Mar 08, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.71

CADD

Benign

7.0

DANN

Benign

0.75

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000051

dbscSNV1_RF

Benign

0.0020

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