chr21-32694317-G-GA

Position:

• chr21-32694317-G-GA

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP6_Moderate BS1

The NM_203446.3(SYNJ1):​c.706-7_706-6insT variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00658 in 1,449,798 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00032 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0073 (0 hom.)
• Consequence: SYNJ1 NM_203446.3 splice_region, splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.65

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 Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 21-32694317-G-GA is Benign according to our data. Variant chr21-32694317-G-GA is described in ClinVar as [Benign]. Clinvar id is 544582.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000319 (48/150248) while in subpopulation EAS AF= 0.00642 (33/5140). AF 95% confidence interval is 0.0047. There are 0 homozygotes in gnomad4. There are 26 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SYNJ1	NM_203446.3	c.706-7_706-6insT		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000674351.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SYNJ1	ENST00000674351.1	c.706-7_706-6insT		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant			NM_203446.3

Frequencies

GnomAD3 genomes AF: 0.000320 AC: 48 AN: 150140 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000244

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00641

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000201

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000445

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00731 AC: 9496 AN: 1299550 Hom.: 0 Cov.: 27 AF XY: 0.00722 AC XY: 4653 AN XY: 644358

Gnomad4 AFR exome AF: 0.00792

Gnomad4 AMR exome AF: 0.00770

Gnomad4 ASJ exome AF: 0.00731

Gnomad4 EAS exome AF: 0.0166

Gnomad4 SAS exome AF: 0.00988

Gnomad4 FIN exome AF: 0.00438

Gnomad4 NFE exome AF: 0.00698

Gnomad4 OTH exome AF: 0.00693

GnomAD4 genome AF: 0.000319 AC: 48 AN: 150248 Hom.: 0 Cov.: 32 AF XY: 0.000355 AC XY: 26 AN XY: 73244

Gnomad4 AFR AF: 0.000244

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00642

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000201

Gnomad4 NFE AF: 0.0000445

Gnomad4 OTH AF: 0.00

Bravo AF: 0.000321

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

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 18, 2024

- -

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs202044634; hg19: chr21-34066627;