rs187016397

chr21-32695050-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

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

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=-0.71).
• 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. This position pass quality control queck.
• BS2: High Homozygotes in GnomAdExome at 18 AR gene

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes AF: 0.000939 AC: 143 AN: 152232 Hom.: 1 Cov.: 32

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.: 18 AF XY: 0.00371 AC XY: 504 AN XY: 135738

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.: 39 Cov.: 30 AF XY: 0.00212 AC XY: 1541 AN XY: 726758

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.: 1 Cov.: 32 AF XY: 0.00117 AC XY: 87 AN XY: 74512

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.: 0

Bravo AF: 0.000597

Asia WGS AF: 0.00433 AC: 15 AN: 3478

EpiCase AF: 0.000273

EpiControl AF: 0.000830

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

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

Other links and lift over

dbSNP: rs187016397; hg19: chr21-34067360;